Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>EPS8L2</italic>
is a new causal gene for childhood onset autosomal recessive progressive hearing loss</title>
<author><name sortKey="Dahmani, Malika" sort="Dahmani, Malika" uniqKey="Dahmani M" first="Malika" last="Dahmani">Malika Dahmani</name>
<affiliation><nlm:aff id="Aff1">Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ammar Khodja, Fatima" sort="Ammar Khodja, Fatima" uniqKey="Ammar Khodja F" first="Fatima" last="Ammar-Khodja">Fatima Ammar-Khodja</name>
<affiliation><nlm:aff id="Aff1">Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bonnet, Crystel" sort="Bonnet, Crystel" uniqKey="Bonnet C" first="Crystel" last="Bonnet">Crystel Bonnet</name>
<affiliation><nlm:aff id="Aff2">Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lefevre, Gaelle M" sort="Lefevre, Gaelle M" uniqKey="Lefevre G" first="Gaelle M." last="Lefèvre">Gaelle M. Lefèvre</name>
<affiliation><nlm:aff id="Aff2">Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hardelin, Jean Pierre" sort="Hardelin, Jean Pierre" uniqKey="Hardelin J" first="Jean-Pierre" last="Hardelin">Jean-Pierre Hardelin</name>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff5">Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, 75015 Paris, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ibrahim, Hassina" sort="Ibrahim, Hassina" uniqKey="Ibrahim H" first="Hassina" last="Ibrahim">Hassina Ibrahim</name>
<affiliation><nlm:aff id="Aff6">Service d’otorhinolaryngologie, Centre Hospitalier Universitaire Mustapha Pacha, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mallek, Zahia" sort="Mallek, Zahia" uniqKey="Mallek Z" first="Zahia" last="Mallek">Zahia Mallek</name>
<affiliation><nlm:aff id="Aff7">Service d’otorhinolaryngologie, Centre Hospitalier Universitaire Bab El Oued, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Petit, Christine" sort="Petit, Christine" uniqKey="Petit C" first="Christine" last="Petit">Christine Petit</name>
<affiliation><nlm:aff id="Aff2">Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff5">Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, 75015 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff8">Collège de France, 75005 Paris, France</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26282398</idno>
<idno type="pmc">4539681</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539681</idno>
<idno type="RBID">PMC:4539681</idno>
<idno type="doi">10.1186/s13023-015-0316-8</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000070</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000070</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>EPS8L2</italic>
is a new causal gene for childhood onset autosomal recessive progressive hearing loss</title>
<author><name sortKey="Dahmani, Malika" sort="Dahmani, Malika" uniqKey="Dahmani M" first="Malika" last="Dahmani">Malika Dahmani</name>
<affiliation><nlm:aff id="Aff1">Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ammar Khodja, Fatima" sort="Ammar Khodja, Fatima" uniqKey="Ammar Khodja F" first="Fatima" last="Ammar-Khodja">Fatima Ammar-Khodja</name>
<affiliation><nlm:aff id="Aff1">Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bonnet, Crystel" sort="Bonnet, Crystel" uniqKey="Bonnet C" first="Crystel" last="Bonnet">Crystel Bonnet</name>
<affiliation><nlm:aff id="Aff2">Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lefevre, Gaelle M" sort="Lefevre, Gaelle M" uniqKey="Lefevre G" first="Gaelle M." last="Lefèvre">Gaelle M. Lefèvre</name>
<affiliation><nlm:aff id="Aff2">Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hardelin, Jean Pierre" sort="Hardelin, Jean Pierre" uniqKey="Hardelin J" first="Jean-Pierre" last="Hardelin">Jean-Pierre Hardelin</name>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff5">Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, 75015 Paris, France</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ibrahim, Hassina" sort="Ibrahim, Hassina" uniqKey="Ibrahim H" first="Hassina" last="Ibrahim">Hassina Ibrahim</name>
<affiliation><nlm:aff id="Aff6">Service d’otorhinolaryngologie, Centre Hospitalier Universitaire Mustapha Pacha, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mallek, Zahia" sort="Mallek, Zahia" uniqKey="Mallek Z" first="Zahia" last="Mallek">Zahia Mallek</name>
<affiliation><nlm:aff id="Aff7">Service d’otorhinolaryngologie, Centre Hospitalier Universitaire Bab El Oued, Algiers, Algeria</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Petit, Christine" sort="Petit, Christine" uniqKey="Petit C" first="Christine" last="Petit">Christine Petit</name>
<affiliation><nlm:aff id="Aff2">Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff3">UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff4">Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff5">Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, 75015 Paris, France</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="Aff8">Collège de France, 75005 Paris, France</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Orphanet Journal of Rare Diseases</title>
<idno type="eISSN">1750-1172</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>More than 70 % of the cases of congenital deafness are of genetic origin, of which approximately 80 % are non-syndromic and show autosomal recessive transmission (DFNB forms). To date, 60 DFNB genes have been identified, most of which cause congenital, severe to profound deafness, whereas a few cause delayed progressive deafness in childhood. We report the study of two Algerian siblings born to consanguineous parents, and affected by progressive hearing loss.</p>
</sec>
<sec><title>Method</title>
<p>After exclusion of <italic>GJB2</italic>
(the gene most frequently involved in non-syndromic deafness in Mediterranean countries), we performed whole-exome sequencing in one sibling.</p>
</sec>
<sec><title>Results</title>
<p>A frame-shift variant (c.1014delC; p.Ser339Alafs*15) was identified in <italic>EPS8L2</italic>
, encoding Epidermal growth factor receptor Pathway Substrate 8 L2, a protein of hair cells’ stereocilia previously implicated in progressive deafness in the mouse. This variant predicts a truncated, inactive protein, or no protein at all owing to nonsense-mediated mRNA decay. It was detected at the homozygous state in the two clinically affected siblings, and at the heterozygous state in the unaffected parents and one unaffected sibling, whereas it was never found in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database.</p>
</sec>
<sec><title>Conclusion</title>
<p>Whole-exome sequencing allowed us to identify a new gene responsible for childhood progressive hearing loss transmitted on the autosomal recessive mode.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Petit, C" uniqKey="Petit C">C Petit</name>
</author>
<author><name sortKey="Levilliers, J" uniqKey="Levilliers J">J Levilliers</name>
</author>
<author><name sortKey="Hardelin, J P" uniqKey="Hardelin J">J-P Hardelin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morton, Ne" uniqKey="Morton N">NE Morton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bitner Glindzicz, M" uniqKey="Bitner Glindzicz M">M Bitner-Glindzicz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Piatto, Vb" uniqKey="Piatto V">VB Piatto</name>
</author>
<author><name sortKey="Secches, Lv" uniqKey="Secches L">LV Secches</name>
</author>
<author><name sortKey="Arroyo, Mas" uniqKey="Arroyo M">MAS Arroyo</name>
</author>
<author><name sortKey="Lopes, Acp" uniqKey="Lopes A">ACP Lopes</name>
</author>
<author><name sortKey="Maniglia, Jv" uniqKey="Maniglia J">JV Maniglia</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Denoyelle, F" uniqKey="Denoyelle F">F Denoyelle</name>
</author>
<author><name sortKey="Marlin, S" uniqKey="Marlin S">S Marlin</name>
</author>
<author><name sortKey="Weil, D" uniqKey="Weil D">D Weil</name>
</author>
<author><name sortKey="Moatti, L" uniqKey="Moatti L">L Moatti</name>
</author>
<author><name sortKey="Chauvin, F" uniqKey="Chauvin F">F Chauvin</name>
</author>
<author><name sortKey="Garabedian, En" uniqKey="Garabedian E">EN Garabedian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Frei, K" uniqKey="Frei K">K Frei</name>
</author>
<author><name sortKey="Ramsebner, R" uniqKey="Ramsebner R">R Ramsebner</name>
</author>
<author><name sortKey="Lucas, T" uniqKey="Lucas T">T Lucas</name>
</author>
<author><name sortKey="Hamader, G" uniqKey="Hamader G">G Hamader</name>
</author>
<author><name sortKey="Szuhai, K" uniqKey="Szuhai K">K Szuhai</name>
</author>
<author><name sortKey="Weipoltshammer, K" uniqKey="Weipoltshammer K">K Weipoltshammer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ammar Khodja, F" uniqKey="Ammar Khodja F">F Ammar-Khodja</name>
</author>
<author><name sortKey="Makrelouf, M" uniqKey="Makrelouf M">M Makrelouf</name>
</author>
<author><name sortKey="Malek, R" uniqKey="Malek R">R Malek</name>
</author>
<author><name sortKey="Ibrahim, H" uniqKey="Ibrahim H">H Ibrahim</name>
</author>
<author><name sortKey="Zenati, A" uniqKey="Zenati A">A Zenati</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Delmaghani, S" uniqKey="Delmaghani S">S Delmaghani</name>
</author>
<author><name sortKey="Aghaie, A" uniqKey="Aghaie A">A Aghaie</name>
</author>
<author><name sortKey="Michalski, N" uniqKey="Michalski N">N Michalski</name>
</author>
<author><name sortKey="Bonnet, C" uniqKey="Bonnet C">C Bonnet</name>
</author>
<author><name sortKey="Weil, D" uniqKey="Weil D">D Weil</name>
</author>
<author><name sortKey="Petit, C" uniqKey="Petit C">C Petit</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Del Castillo, Fj" uniqKey="Del Castillo F">FJ del Castillo</name>
</author>
<author><name sortKey="Rodriguez Allesteros, M" uniqKey="Rodriguez Allesteros M">M Rodriguez‐Ballesteros</name>
</author>
<author><name sortKey="Alvarez, A" uniqKey="Alvarez A">A Alvarez</name>
</author>
<author><name sortKey="Hutchin, T" uniqKey="Hutchin T">T Hutchin</name>
</author>
<author><name sortKey="Leonardi, E" uniqKey="Leonardi E">E Leonardi</name>
</author>
<author><name sortKey="De Oliveira, Ca" uniqKey="De Oliveira C">CA de Oliveira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Furness, Dn" uniqKey="Furness D">DN Furness</name>
</author>
<author><name sortKey="Johnson, Sl" uniqKey="Johnson S">SL Johnson</name>
</author>
<author><name sortKey="Manor, U" uniqKey="Manor U">U Manor</name>
</author>
<author><name sortKey="Ruttiger, L" uniqKey="Ruttiger L">L Ruttiger</name>
</author>
<author><name sortKey="Tocchetti, A" uniqKey="Tocchetti A">A Tocchetti</name>
</author>
<author><name sortKey="Offenhauser, N" uniqKey="Offenhauser N">N Offenhauser</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abe, S" uniqKey="Abe S">S Abe</name>
</author>
<author><name sortKey="Usami, S" uniqKey="Usami S">S Usami</name>
</author>
<author><name sortKey="Hoover, Dm" uniqKey="Hoover D">DM Hoover</name>
</author>
<author><name sortKey="Cohn, E" uniqKey="Cohn E">E Cohn</name>
</author>
<author><name sortKey="Shinkawa, H" uniqKey="Shinkawa H">H Shinkawa</name>
</author>
<author><name sortKey="Kimberling, Wj" uniqKey="Kimberling W">WJ Kimberling</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bladwin, Ct" uniqKey="Bladwin C">CT Bladwin</name>
</author>
<author><name sortKey="Weiss, S" uniqKey="Weiss S">S Weiss</name>
</author>
<author><name sortKey="Farrer, La" uniqKey="Farrer L">LA Farrer</name>
</author>
<author><name sortKey="De Stefano, Al" uniqKey="De Stefano A">AL De Stefano</name>
</author>
<author><name sortKey="Adair, R" uniqKey="Adair R">R Adair</name>
</author>
<author><name sortKey="Franklyn, B" uniqKey="Franklyn B">B Franklyn</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walsh, T" uniqKey="Walsh T">T Walsh</name>
</author>
<author><name sortKey="Walsh, V" uniqKey="Walsh V">V Walsh</name>
</author>
<author><name sortKey="Vreugde, S" uniqKey="Vreugde S">S Vreugde</name>
</author>
<author><name sortKey="Hertzano, R" uniqKey="Hertzano R">R Hertzano</name>
</author>
<author><name sortKey="Shahin, H" uniqKey="Shahin H">H Shahin</name>
</author>
<author><name sortKey="Haika, S" uniqKey="Haika S">S Haika</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Grillet, N" uniqKey="Grillet N">N Grillet</name>
</author>
<author><name sortKey="Schwander, M" uniqKey="Schwander M">M Schwander</name>
</author>
<author><name sortKey="Hildebrand, Ms" uniqKey="Hildebrand M">MS Hildebrand</name>
</author>
<author><name sortKey="Sczaniecka, A" uniqKey="Sczaniecka A">A Sczaniecka</name>
</author>
<author><name sortKey="Kolatkar, A" uniqKey="Kolatkar A">A Kolatkar</name>
</author>
<author><name sortKey="Velasco, J" uniqKey="Velasco J">J Velasco</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Delmaghani, S" uniqKey="Delmaghani S">S Delmaghani</name>
</author>
<author><name sortKey="Del Castillo, Fg" uniqKey="Del Castillo F">FG del Castillo</name>
</author>
<author><name sortKey="Michel, V" uniqKey="Michel V">V Michel</name>
</author>
<author><name sortKey="Leibovici, M" uniqKey="Leibovici M">M Leibovici</name>
</author>
<author><name sortKey="Aghaie, A" uniqKey="Aghaie A">A Aghaie</name>
</author>
<author><name sortKey="Ron, U" uniqKey="Ron U">U Ron</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schwander, M" uniqKey="Schwander M">M Schwander</name>
</author>
<author><name sortKey="Sczaniecka, A" uniqKey="Sczaniecka A">A Sczaniecka</name>
</author>
<author><name sortKey="Grillet, N" uniqKey="Grillet N">N Grillet</name>
</author>
<author><name sortKey="Bailey, Js" uniqKey="Bailey J">JS Bailey</name>
</author>
<author><name sortKey="Avenarius, M" uniqKey="Avenarius M">M Avenarius</name>
</author>
<author><name sortKey="Najmabadi, H" uniqKey="Najmabadi H">H Najmabadi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ebermann, I" uniqKey="Ebermann I">I Ebermann</name>
</author>
<author><name sortKey="Walger, M" uniqKey="Walger M">M Walger</name>
</author>
<author><name sortKey="Scholl, Hpn" uniqKey="Scholl H">HPN Scholl</name>
</author>
<author><name sortKey="Issa, Pc" uniqKey="Issa P">PC Issa</name>
</author>
<author><name sortKey="Luke, C" uniqKey="Luke C">C Luke</name>
</author>
<author><name sortKey="Nurnberg, G" uniqKey="Nurnberg G">G Nurnberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chaleshtori, Mh" uniqKey="Chaleshtori M">MH Chaleshtori</name>
</author>
<author><name sortKey="Simpson, Ma" uniqKey="Simpson M">MA Simpson</name>
</author>
<author><name sortKey="Farrokhi, E" uniqKey="Farrokhi E">E Farrokhi</name>
</author>
<author><name sortKey="Dolati, M" uniqKey="Dolati M">M Dolati</name>
</author>
<author><name sortKey="Rad, Lh" uniqKey="Rad L">LH Rad</name>
</author>
<author><name sortKey="Geshnigani, Sa" uniqKey="Geshnigani S">SA Geshnigani</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Collin, Rwj" uniqKey="Collin R">RWJ Collin</name>
</author>
<author><name sortKey="Kalay, E" uniqKey="Kalay E">E Kalay</name>
</author>
<author><name sortKey="Oostrik, J" uniqKey="Oostrik J">J Oostrik</name>
</author>
<author><name sortKey="Caylan, R" uniqKey="Caylan R">R Caylan</name>
</author>
<author><name sortKey="Wollnik, B" uniqKey="Wollnik B">B Wollnik</name>
</author>
<author><name sortKey="Arslan, S" uniqKey="Arslan S">S Arslan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Huang, M" uniqKey="Huang M">M Huang</name>
</author>
<author><name sortKey="Duman, D" uniqKey="Duman D">D Duman</name>
</author>
<author><name sortKey="Cengiz, Fb" uniqKey="Cengiz F">FB Cengiz</name>
</author>
<author><name sortKey="Bademci, G" uniqKey="Bademci G">G Bademci</name>
</author>
<author><name sortKey="Tokgoz Yilmaz, S" uniqKey="Tokgoz Yilmaz S">S Tokgöz-Yilmaz</name>
</author>
<author><name sortKey="Hi Mi, B" uniqKey="Hi Mi B">B Hişmi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rehman, Au" uniqKey="Rehman A">AU Rehman</name>
</author>
<author><name sortKey="Morell, Rj" uniqKey="Morell R">RJ Morell</name>
</author>
<author><name sortKey="Belyantseva, Ia" uniqKey="Belyantseva I">IA Belyantseva</name>
</author>
<author><name sortKey="Khan, Sy" uniqKey="Khan S">SY Khan</name>
</author>
<author><name sortKey="Boger, Et" uniqKey="Boger E">ET Boger</name>
</author>
<author><name sortKey="Shahzad, M" uniqKey="Shahzad M">M Shahzad</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name>
</author>
<author><name sortKey="Pohl, E" uniqKey="Pohl E">E Pohl</name>
</author>
<author><name sortKey="Boulouiz, R" uniqKey="Boulouiz R">R Boulouiz</name>
</author>
<author><name sortKey="Schraders, M" uniqKey="Schraders M">M Schraders</name>
</author>
<author><name sortKey="Nurnberg, G" uniqKey="Nurnberg G">G Nurnberg</name>
</author>
<author><name sortKey="Charif, M" uniqKey="Charif M">M Charif</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Veske, A" uniqKey="Veske A">A Veske</name>
</author>
<author><name sortKey="Oehlmann, R" uniqKey="Oehlmann R">R Oehlmann</name>
</author>
<author><name sortKey="Younus, F" uniqKey="Younus F">F Younus</name>
</author>
<author><name sortKey="Mohyuddin, A" uniqKey="Mohyuddin A">A Mohyuddin</name>
</author>
<author><name sortKey="Muller Myhsok, B" uniqKey="Muller Myhsok B">B Müller-Myhsok</name>
</author>
<author><name sortKey="Qasim Mehdi, S" uniqKey="Qasim Mehdi S">S Qasim Mehdi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Scott, Hs" uniqKey="Scott H">HS Scott</name>
</author>
<author><name sortKey="Kudoh, J" uniqKey="Kudoh J">J Kudoh</name>
</author>
<author><name sortKey="Wattenhofer, M" uniqKey="Wattenhofer M">M Wattenhofer</name>
</author>
<author><name sortKey="Shibuya, K" uniqKey="Shibuya K">K Shibuya</name>
</author>
<author><name sortKey="Berry, A" uniqKey="Berry A">A Berry</name>
</author>
<author><name sortKey="Chrast, R" uniqKey="Chrast R">R Chrast</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Charizopoulou, N" uniqKey="Charizopoulou N">N Charizopoulou</name>
</author>
<author><name sortKey="Lelli, A" uniqKey="Lelli A">A Lelli</name>
</author>
<author><name sortKey="Schraders, M" uniqKey="Schraders M">M Schraders</name>
</author>
<author><name sortKey="Ray, K" uniqKey="Ray K">K Ray</name>
</author>
<author><name sortKey="Hildebrand, Ms" uniqKey="Hildebrand M">MS Hildebrand</name>
</author>
<author><name sortKey="Ramesh, A" uniqKey="Ramesh A">A Ramesh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Horn, Hf" uniqKey="Horn H">HF Horn</name>
</author>
<author><name sortKey="Brownstein, Z" uniqKey="Brownstein Z">Z Brownstein</name>
</author>
<author><name sortKey="Lenz, Dr" uniqKey="Lenz D">DR Lenz</name>
</author>
<author><name sortKey="Shivatzki, S" uniqKey="Shivatzki S">S Shivatzki</name>
</author>
<author><name sortKey="Dror, Aa" uniqKey="Dror A">AA Dror</name>
</author>
<author><name sortKey="Dagan Rosenfeld, O" uniqKey="Dagan Rosenfeld O">O Dagan-Rosenfeld</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Imtiaz, A" uniqKey="Imtiaz A">A Imtiaz</name>
</author>
<author><name sortKey="Kohrman, Dc" uniqKey="Kohrman D">DC Kohrman</name>
</author>
<author><name sortKey="Naz, Sa" uniqKey="Naz S">SA Naz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Seco, Cz" uniqKey="Seco C">CZ Seco</name>
</author>
<author><name sortKey="Oonk, Am" uniqKey="Oonk A">AM Oonk</name>
</author>
<author><name sortKey="Dom Nguez Ruiz, M" uniqKey="Dom Nguez Ruiz M">M Domınguez-Ruiz</name>
</author>
<author><name sortKey="Draaisma, Jmt" uniqKey="Draaisma J">JMT Draaisma</name>
</author>
<author><name sortKey="Gandi, M" uniqKey="Gandi M">M Gandi</name>
</author>
<author><name sortKey="Oostrik, J" uniqKey="Oostrik J">J Oostrik</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Heer, Am" uniqKey="De Heer A">AM de Heer</name>
</author>
<author><name sortKey="Collin, Rw" uniqKey="Collin R">RW Collin</name>
</author>
<author><name sortKey="Huygen, Pl" uniqKey="Huygen P">PL Huygen</name>
</author>
<author><name sortKey="Schraders, M" uniqKey="Schraders M">M Schraders</name>
</author>
<author><name sortKey="Oostrik, J" uniqKey="Oostrik J">J Oostrik</name>
</author>
<author><name sortKey="Rouwette, M" uniqKey="Rouwette M">M Rouwette</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Offenh User, N" uniqKey="Offenh User N">N Offenhäuser</name>
</author>
<author><name sortKey="Borgonovo, A" uniqKey="Borgonovo A">A Borgonovo</name>
</author>
<author><name sortKey="Disanza, A" uniqKey="Disanza A">A Disanza</name>
</author>
<author><name sortKey="Romano, P" uniqKey="Romano P">P Romano</name>
</author>
<author><name sortKey="Ponzanelli, I" uniqKey="Ponzanelli I">I Ponzanelli</name>
</author>
<author><name sortKey="Iannolo, G" uniqKey="Iannolo G">G Iannolo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zampini, V" uniqKey="Zampini V">V Zampini</name>
</author>
<author><name sortKey="Ruttiger, L" uniqKey="Ruttiger L">L Ruttiger</name>
</author>
<author><name sortKey="Johnson, Sl" uniqKey="Johnson S">SL Johnson</name>
</author>
<author><name sortKey="Franz, C" uniqKey="Franz C">C Franz</name>
</author>
<author><name sortKey="Furness, Dn" uniqKey="Furness D">DN Furness</name>
</author>
<author><name sortKey="Waldhaus, J" uniqKey="Waldhaus J">J Waldhaus</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Behlouli, A" uniqKey="Behlouli A">A Behlouli</name>
</author>
<author><name sortKey="Bonnet, C" uniqKey="Bonnet C">C Bonnet</name>
</author>
<author><name sortKey="Abdi, S" uniqKey="Abdi S">S Abdi</name>
</author>
<author><name sortKey="Bouaita, A" uniqKey="Bouaita A">A Bouaita</name>
</author>
<author><name sortKey="Lelli, A" uniqKey="Lelli A">A Lelli</name>
</author>
<author><name sortKey="Hardelin, J P" uniqKey="Hardelin J">J-P Hardelin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Manor, U" uniqKey="Manor U">U Manor</name>
</author>
<author><name sortKey="Disanza, A" uniqKey="Disanza A">A Disanza</name>
</author>
<author><name sortKey="Grati, Mh" uniqKey="Grati M">MH Grati</name>
</author>
<author><name sortKey="Andrade, L" uniqKey="Andrade L">L Andrade</name>
</author>
<author><name sortKey="Lin, H" uniqKey="Lin H">H Lin</name>
</author>
<author><name sortKey="Di Fiore, Pp" uniqKey="Di Fiore P">PP Di Fiore</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Orphanet J Rare Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">Orphanet J Rare Dis</journal-id>
<journal-title-group><journal-title>Orphanet Journal of Rare Diseases</journal-title>
</journal-title-group>
<issn pub-type="epub">1750-1172</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26282398</article-id>
<article-id pub-id-type="pmc">4539681</article-id>
<article-id pub-id-type="publisher-id">316</article-id>
<article-id pub-id-type="doi">10.1186/s13023-015-0316-8</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title><italic>EPS8L2</italic>
is a new causal gene for childhood onset autosomal recessive progressive hearing loss</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Dahmani</surname>
<given-names>Malika</given-names>
</name>
<address><email>malikadahmani.usthb@gmail.com</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ammar-Khodja</surname>
<given-names>Fatima</given-names>
</name>
<address><email>fatima.khodja@gmail.com</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bonnet</surname>
<given-names>Crystel</given-names>
</name>
<address><email>crystel.bonnet@inserm.fr</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lefèvre</surname>
<given-names>Gaelle M.</given-names>
</name>
<address><email>gaelle.lefevre@inserm.fr</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hardelin</surname>
<given-names>Jean-Pierre</given-names>
</name>
<address><email>jean-pierre.hardelin@pasteur.fr</email>
</address>
<xref ref-type="aff" rid="Aff3"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
<xref ref-type="aff" rid="Aff5"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ibrahim</surname>
<given-names>Hassina</given-names>
</name>
<address><email>ibrahim.hassina@yahoo.fr</email>
</address>
<xref ref-type="aff" rid="Aff6"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mallek</surname>
<given-names>Zahia</given-names>
</name>
<address><email>kacizahra@yahoo.fr</email>
</address>
<xref ref-type="aff" rid="Aff7"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Petit</surname>
<given-names>Christine</given-names>
</name>
<address><email>christine.petit@pasteur.fr</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
<xref ref-type="aff" rid="Aff5"></xref>
<xref ref-type="aff" rid="Aff8"></xref>
</contrib>
<aff id="Aff1"><label></label>
Equipe de Génétique, Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumédiène (USTHB), El Alia, Bab-Ezzouar, Algiers, Algeria</aff>
<aff id="Aff2"><label></label>
Syndrome de Usher et autres Atteintes Rétino-Cochléaires, Institut de la vision, 75012 Paris, France</aff>
<aff id="Aff3"><label></label>
UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France</aff>
<aff id="Aff4"><label></label>
Sorbonne Universités, UPMC Université Paris 06, Complexité du Vivant, Paris, 75252 Cedex 05 France</aff>
<aff id="Aff5"><label></label>
Unité de Génétique et Physiologie de l’Audition, Institut Pasteur, 75015 Paris, France</aff>
<aff id="Aff6"><label></label>
Service d’otorhinolaryngologie, Centre Hospitalier Universitaire Mustapha Pacha, Algiers, Algeria</aff>
<aff id="Aff7"><label></label>
Service d’otorhinolaryngologie, Centre Hospitalier Universitaire Bab El Oued, Algiers, Algeria</aff>
<aff id="Aff8"><label></label>
Collège de France, 75005 Paris, France</aff>
</contrib-group>
<pub-date pub-type="epub"><day>19</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>19</day>
<month>8</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection"><year>2015</year>
</pub-date>
<volume>10</volume>
<elocation-id>96</elocation-id>
<history><date date-type="received"><day>28</day>
<month>4</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>3</day>
<month>8</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© Dahmani et al. 2015</copyright-statement>
<license license-type="OpenAccess"><license-p><bold> Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p>More than 70 % of the cases of congenital deafness are of genetic origin, of which approximately 80 % are non-syndromic and show autosomal recessive transmission (DFNB forms). To date, 60 DFNB genes have been identified, most of which cause congenital, severe to profound deafness, whereas a few cause delayed progressive deafness in childhood. We report the study of two Algerian siblings born to consanguineous parents, and affected by progressive hearing loss.</p>
</sec>
<sec><title>Method</title>
<p>After exclusion of <italic>GJB2</italic>
(the gene most frequently involved in non-syndromic deafness in Mediterranean countries), we performed whole-exome sequencing in one sibling.</p>
</sec>
<sec><title>Results</title>
<p>A frame-shift variant (c.1014delC; p.Ser339Alafs*15) was identified in <italic>EPS8L2</italic>
, encoding Epidermal growth factor receptor Pathway Substrate 8 L2, a protein of hair cells’ stereocilia previously implicated in progressive deafness in the mouse. This variant predicts a truncated, inactive protein, or no protein at all owing to nonsense-mediated mRNA decay. It was detected at the homozygous state in the two clinically affected siblings, and at the heterozygous state in the unaffected parents and one unaffected sibling, whereas it was never found in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database.</p>
</sec>
<sec><title>Conclusion</title>
<p>Whole-exome sequencing allowed us to identify a new gene responsible for childhood progressive hearing loss transmitted on the autosomal recessive mode.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>Epidermal growth factor receptor pathway Substrate 8 L2 (EPS8L2)</kwd>
<kwd>Progressive deafness</kwd>
<kwd>Whole-exome sequencing</kwd>
<kwd>Stereocilia bundle</kwd>
</kwd-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2015</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body><sec id="Sec1" sec-type="introduction"><title>Background</title>
<p>Deafness is the most common sensory deficit in humans, with an incidence of 1 in 700 live births. It is estimated that about two thirds of prelingual severe to profound isolated (non-syndromic) deafness cases have a genetic cause in developed countries [<xref ref-type="bibr" rid="CR1">1</xref>
], and autosomal recessive inheritance (DFNB) accounts for 80 % of the genetic cases [<xref ref-type="bibr" rid="CR2">2</xref>
]. Cases with autosomal recessive non-syndromic hearing loss (ARNSHL) are more prevalent in populations where consanguineous marriages are common, including Maghrebi populations. To date, 60 DFNB genes have been identified (<ext-link ext-link-type="uri" xlink:href="http://hereditaryhearingloss.org/">http://hereditaryhearingloss.org/</ext-link>
). Recessive deafness is usually prelingual, severe or profound, and fully penetrant, but some DFNB genes cause progressive hearing loss with delayed onset in childhood [<xref ref-type="bibr" rid="CR3">3</xref>
, <xref ref-type="bibr" rid="CR4">4</xref>
].</p>
<p>In Algeria, mutations in <italic>GJB2</italic>
, encoding connexin 26 (Gap Junction Protein Beta 2), account for no less than 35 % of the cases [<xref ref-type="bibr" rid="CR5">5</xref>
–<xref ref-type="bibr" rid="CR7">7</xref>
]. Mutations in other DFNB genes have also been identified, which illustrates the ARNSHL genetic heterogeneity in this population [<xref ref-type="bibr" rid="CR8">8</xref>
]. However, the genetic bases of progressive deafness beginning in childhood have not been characterized yet. Here, we report the identification, by whole-exome sequencing (WES), of a new causal gene for recessively inherited progressive deafness in an Algerian family.</p>
</sec>
<sec id="Sec2" sec-type="materials|methods"><title>Patients and methods</title>
<sec id="Sec3"><title>Patients</title>
<p>The two affected siblings were recruited in deafness schools of Blida and Baraki in Algiers (Algeria), and clinically examined in the otorhinolaryngology department at Bab El Oued hospital in Algiers. Medical history and physical examination of the patients did not reveal any non-genetic cause for the deafness and confirmed its non-syndromic nature. Hearing thresholds were determined by pure tone audiometry between 125 Hz and 8000 Hz, using air-conduction and bone conduction of sound.</p>
</sec>
<sec id="Sec4"><title>Methods</title>
<p>The study was approved by the local Ethics Committee and the Committee for the Protection of Individuals in Biochemical Research as required by French legislation. A written consent for genetic testing was obtained from every family member. DNA was extracted from peripheral blood lymphocytes using the Promega Wizard Genomic DNA Purification Kit (Promega, Madison, MI, USA, Cat. # A1120). Whole-exome sequencing and bioinformatic analysis were carried out as previously described [<xref ref-type="bibr" rid="CR9">9</xref>
]. To validate the mutation in <italic>EPS8L2</italic>
, sequencing of exon 12 was performed by the Sanger technique with the following primers: EPS8L2-12 F 5′-GTCTGTGCTGAGGGGAGG-3′ and EPS8L2-12R 5′-CTCTCCAGAACTGGCCCAC-3′ (<ext-link ext-link-type="uri" xlink:href="http://bioinfo.ut.ee/primer3-0.4.0/primer3/">http://bioinfo.ut.ee/primer3-0.4.0/primer3/</ext-link>
).</p>
</sec>
</sec>
<sec id="Sec5" sec-type="discussion"><title>Results and discussion</title>
<p>We studied an Algerian family with two siblings (IV.1 and IV.2) presenting with ARNSHI (Fig. <xref rid="Fig1" ref-type="fig">1a</xref>
). The two affected children were born to normal hearing second-cousin parents, and reportedly had normal hearing for the first 3 years. The first signs of hearing impairment appeared around 4 years of age. By 6 years of age, they presented a bilateral elevation of the hearing threshold, starting at 30 dB at low frequencies (125 Hz) and increasing steadily up to 90 dB at high frequencies (8000 Hz) (Fig. <xref rid="Fig1" ref-type="fig">1b</xref>
). At the age of 10, the hearing threshold increased further at all frequencies, ranging from 40 dB at 125 Hz, up to 100 dB at 8000 Hz (Fig. <xref rid="Fig1" ref-type="fig">1b</xref>
and data not shown). Of note, audiograms showing parallel slopes at 6 and 10 years of age are rather unusual.<fig id="Fig1"><label>Fig. 1</label>
<caption><p>Clinical and molecular data of the patients harboring a biallelic homozygous frameshift mutation in <italic>EPS8L2</italic>
. <bold>a</bold>
Pedigree showing the segregation of the mutation in the family. The + and – signs denote the wild type and mutant alleles, respectively. The two clinically affected siblings are indicated by black symbols. The double horizontal bar joining the parents in generation III indicates consanguinity. <bold>b</bold>
Air-conduction audiometric curves for patient IV.2 at the ages of 6 (open symbols) and 10 (black symbols) years of age. For each pure tone frequency tested (from 0.25 to 8 kHz), the hearing thresholds (in dB HL) for the right and left ears are indicated with circles and diamonds, respectively. <bold>c</bold>
DNA sequencing chromatograms showing the mutation (arrow). <bold>d</bold>
Schematic representation of the human EPS8L2 protein. The protein (715 amino acids) contains a phosphotyrosine interaction domain (PID), an SRC Homology 3 (SH3) domain, and an effector region (46 % of amino acid sequence identity with F-actin binding domain of EPS8) including a sterile alpha motif/pointed domain (SAM/PNT)</p>
</caption>
<graphic xlink:href="13023_2015_316_Fig1_HTML" id="MO1"></graphic>
</fig>
</p>
<p>First, we explored the possibility of mutations in <italic>GJB2</italic>
by Sanger sequencing of the non-coding exon and the single coding exon of this gene for each patient, and screened the patients for the common deletion reported in the promoter region [<xref ref-type="bibr" rid="CR10">10</xref>
]. Since no mutations were found, we then proceeded to sequence the whole exome of patient IV.2, and looked for homozygous, compound heterozygous, or heterozygous variants with a predicted pathogenicity. None of the genes known to cause autosomal recessive or autosomal dominant forms of deafness showed any such variants in coding and non-coding exons or splice sites. The <italic>STRC</italic>
and <italic>OTOA</italic>
genes, which were poorly covered by WES, were further analyzed by single nucleotide polymorphism (SNP) array and q-PCR. No evidence for genomic rearrangement was found. Variants with a prevalence superior to 0.01 % in the DBSNP132, 1000 genomes, HapMap, and Exome Variant Server databases were excluded. Given the parents' consanguinity, the causal mutation was searched preferentially among homozygous nonsense, frame-shift, splice site, and missense variants. From the originally-identified 75,753 SNPs and 5918 insertions/deletions, only 5 SNPs and 1 deletion (Table <xref rid="Tab1" ref-type="table">1</xref>
) appeared as good candidates. The four missense variants and the synonymous/splice exon variant were deemed non pathogenic by the prediction algorithms SIFT, PolyPhen2, Mutation Taster and Nnsplice. In contrast, the homozygous 1-bp deletion c.1014delC (p.Ser339Alafs*15), located in exon 12 of the <italic>EPS8L2</italic>
gene, was predicted to cause a frame shift leading to premature termination of translation<italic>.</italic>
The causal role of this variant was further supported by prior work showing that inactivation of this gene in the mouse caused progressive deafness [<xref ref-type="bibr" rid="CR11">11</xref>
]. After Sanger sequencing of <italic>EPS8L2</italic>
exon 12 of the two affected children, the unaffected sister, and the parents, the segregation analysis confirmed that the mutation was homozygous only in the deaf children, whereas the parents and the unaffected sibling were heterozygous for this variant (Fig. <xref rid="Fig1" ref-type="fig">1a, c</xref>
). Lastly, the variant was never detected in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database. We concluded that this frame-shift mutation, predicted to result either in a truncated inactive protein, or in no protein at all due to nonsense-mediated mRNA decay, is responsible for the progressive hearing loss of the two Algerian patients. <italic>EPS8L2</italic>
can thus be added to the list of DFNB genes already reported to cause progressive ARNSHL in humans: <italic>SLC26A4</italic>
[<xref ref-type="bibr" rid="CR12">12</xref>
, <xref ref-type="bibr" rid="CR13">13</xref>
], <italic>MYO3A</italic>
[<xref ref-type="bibr" rid="CR14">14</xref>
], <italic>LOXHD1</italic>
[<xref ref-type="bibr" rid="CR15">15</xref>
], <italic>PJVK</italic>
[<xref ref-type="bibr" rid="CR16">16</xref>
–<xref ref-type="bibr" rid="CR20">20</xref>
], <italic>SERPINB6</italic>
[<xref ref-type="bibr" rid="CR21">21</xref>
], <italic>TPRN</italic>
[<xref ref-type="bibr" rid="CR22">22</xref>
, <xref ref-type="bibr" rid="CR23">23</xref>
], <italic>TMPRSS3</italic>
[<xref ref-type="bibr" rid="CR24">24</xref>
, <xref ref-type="bibr" rid="CR25">25</xref>
], <italic>GIPC3</italic>
[<xref ref-type="bibr" rid="CR26">26</xref>
], <italic>SYNE4</italic>
[<xref ref-type="bibr" rid="CR27">27</xref>
], <italic>GRXCR2</italic>
[<xref ref-type="bibr" rid="CR28">28</xref>
], <italic>CLIC5</italic>
[<xref ref-type="bibr" rid="CR29">29</xref>
], <italic>TMC1</italic>
[<xref ref-type="bibr" rid="CR30">30</xref>
], <italic>GRXCR1</italic>
[<xref ref-type="bibr" rid="CR31">31</xref>
], and <italic>LRTOMT</italic>
[<xref ref-type="bibr" rid="CR32">32</xref>
]. Of note, about 25 % of the DFNB genes identified so far are responsible for progressive forms of deafness, and several of them (<italic>SLC26A4</italic>
, <italic>LOXHD1</italic>
, <italic>PJVK</italic>
, <italic>TMPRSS3</italic>
, <italic>GIPC3</italic>
, <italic>TMC1</italic>
, <italic>GRXCR1, LRTOMT</italic>
) can cause either non-progressive or progressive forms of deafness.<table-wrap id="Tab1"><label>Table 1</label>
<caption><p>Analysis of Indel and SNP files showing the variants found in the homozygous state in patient IV.2</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th>Gene name</th>
<th>Refseq</th>
<th>Type of variant</th>
<th>Mutation</th>
<th>Exon #</th>
</tr>
</thead>
<tbody><tr><td><italic>ATAD5</italic>
</td>
<td>NM_024857.3</td>
<td>missense</td>
<td>c.643G > A; p.Asp215Asn</td>
<td>2</td>
</tr>
<tr><td><italic>CDRT1</italic>
</td>
<td>NM_006382.3</td>
<td>synonymous/splice</td>
<td>c.1848A > G; p.Lys616Lys</td>
<td>11</td>
</tr>
<tr><td><italic>EPS8L2</italic>
</td>
<td>NM_022772.3</td>
<td>frame-shift</td>
<td>c.1014delC; p.Ser339Alafs*15</td>
<td>12</td>
</tr>
<tr><td><italic>NLRP6</italic>
</td>
<td>NM_138329.1</td>
<td>missense</td>
<td>c.2138C > T; p.Ala713Val</td>
<td>5</td>
</tr>
<tr><td><italic>OR51V1</italic>
</td>
<td>NM_001004760.2</td>
<td>missense</td>
<td>c.631C > G; p.Leu211Val</td>
<td>1</td>
</tr>
<tr><td><italic>TOLLIP</italic>
</td>
<td>NM_019009.3</td>
<td>missense</td>
<td>c.481G > A; p.Asp161Asn</td>
<td>4</td>
</tr>
</tbody>
</table>
</table-wrap>
</p>
<p><italic>EPS8L2</italic>
has 24 exons and codes for a 715 amino acid protein (Fig. <xref rid="Fig1" ref-type="fig">1d</xref>
), which is a member of the actin-binding protein EPS8 (epidermal growth factor receptor pathway substrate 8) family. This family includes four members, EPS8 and the three EPS8-like proteins (EPS8L1, EPS8L2, and EPS8L3), with partially overlapping functions [<xref ref-type="bibr" rid="CR33">33</xref>
]. In the mouse ear, EPS8L2 was detected at the stereocilia tips of both cochlear and vestibular hair cells. <italic>Eps8L2</italic>
knockout mice undergo progressive hearing loss, as the result of the progressive disorganization of the hair bundles of both inner and outer hair cells. Scanning electron microscopy analysis of the hair bundles in the cochlea of these mice showed that stereocilia of the tall row are shorter and fewer than those of wild-type mice, whereas both the middle and small stereocilia rows seem to be preserved and unaffected [<xref ref-type="bibr" rid="CR11">11</xref>
]. By contrast, mutations in the EPS8 gene cause profound congenital deafness in mice and humans [<xref ref-type="bibr" rid="CR34">34</xref>
, <xref ref-type="bibr" rid="CR35">35</xref>
]. In the mouse cochlea, <italic>Eps8</italic>
is essential for the initial elongation of stereocilia [<xref ref-type="bibr" rid="CR34">34</xref>
, <xref ref-type="bibr" rid="CR36">36</xref>
], whereas <italic>Eps8L2</italic>
is required for their maintenance in mature hair cells [<xref ref-type="bibr" rid="CR11">11</xref>
].</p>
</sec>
<sec id="Sec6" sec-type="conclusion"><title>Conclusion</title>
<p>Deafness is a highly heterogeneous disorder, and many causative genes still remain to be identified. Here, despite several limitations (e.g. only a single family possibly analysed, uneven exon coverage at certain loci by WES), we were able to identify a new pathogenic variant responsible for ARNSHL in two Algerian siblings, by combining the powers of WES and genetics. This report is the first to incriminate <italic>EPS8L2</italic>
, a gene formerly known to cause deafness in rodents, as a causal gene for progressive hearing loss in humans.</p>
</sec>
</body>
<back><fn-group><fn><p><bold>Competing interests</bold>
</p>
<p>The authors declare that they have no competing interests.</p>
</fn>
<fn><p><bold>Authors’ contributions</bold>
</p>
<p>FAK and CP designed the project. MD and CB analysed WES and Sanger sequencing results. HI and ZM contributed to clinical evaluation of the patients. MD, FAK, CB, GML, JPH, and CP wrote the article. All authors read and approved the final manuscript.</p>
</fn>
</fn-group>
<ack><p>We thank all the family members for their participation in the study. This work was supported by grants from the Algerian government, the BNP Paribas Foundation, the French LABEX LIFESENSES grant [reference ANR-10-LABX-65], and the Pasteur-Weizmann program.</p>
</ack>
<ref-list id="Bib1"><title>References</title>
<ref id="CR1"><label>1.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Petit</surname>
<given-names>C</given-names>
</name>
<name><surname>Levilliers</surname>
<given-names>J</given-names>
</name>
<name><surname>Hardelin</surname>
<given-names>J-P</given-names>
</name>
</person-group>
<article-title>Molecular genetics of hearing loss</article-title>
<source>Annu Rev Genet</source>
<year>2001</year>
<volume>35</volume>
<fpage>589</fpage>
<lpage>646</lpage>
<pub-id pub-id-type="doi">10.1146/annurev.genet.35.102401.091224</pub-id>
<pub-id pub-id-type="pmid">11700295</pub-id>
</element-citation>
</ref>
<ref id="CR2"><label>2.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Morton</surname>
<given-names>NE</given-names>
</name>
</person-group>
<article-title>Genetic epidemiology of hearing impairment</article-title>
<source>Annu NY Acad Sci</source>
<year>1991</year>
<volume>630</volume>
<fpage>16</fpage>
<lpage>31</lpage>
<pub-id pub-id-type="doi">10.1111/j.1749-6632.1991.tb19572.x</pub-id>
</element-citation>
</ref>
<ref id="CR3"><label>3.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bitner-Glindzicz</surname>
<given-names>M</given-names>
</name>
</person-group>
<article-title>Hereditary deafness and phenotyping in humans</article-title>
<source>Br Med Bull</source>
<year>2002</year>
<volume>63</volume>
<fpage>73</fpage>
<lpage>94</lpage>
<pub-id pub-id-type="doi">10.1093/bmb/63.1.73</pub-id>
<pub-id pub-id-type="pmid">12324385</pub-id>
</element-citation>
</ref>
<ref id="CR4"><label>4.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Piatto</surname>
<given-names>VB</given-names>
</name>
<name><surname>Secches</surname>
<given-names>LV</given-names>
</name>
<name><surname>Arroyo</surname>
<given-names>MAS</given-names>
</name>
<name><surname>Lopes</surname>
<given-names>ACP</given-names>
</name>
<name><surname>Maniglia</surname>
<given-names>JV</given-names>
</name>
</person-group>
<article-title>Nonsyndromic deafness - Molecular update</article-title>
<source>Open Biol J</source>
<year>2009</year>
<volume>2</volume>
<fpage>80</fpage>
<lpage>90</lpage>
<pub-id pub-id-type="doi">10.2174/1874196700902010080</pub-id>
</element-citation>
</ref>
<ref id="CR5"><label>5.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Denoyelle</surname>
<given-names>F</given-names>
</name>
<name><surname>Marlin</surname>
<given-names>S</given-names>
</name>
<name><surname>Weil</surname>
<given-names>D</given-names>
</name>
<name><surname>Moatti</surname>
<given-names>L</given-names>
</name>
<name><surname>Chauvin</surname>
<given-names>F</given-names>
</name>
<name><surname>Garabedian</surname>
<given-names>EN</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling</article-title>
<source>Lancet</source>
<year>1999</year>
<volume>353</volume>
<fpage>1298</fpage>
<lpage>1303</lpage>
<pub-id pub-id-type="doi">10.1016/S0140-6736(98)11071-1</pub-id>
<pub-id pub-id-type="pmid">10218527</pub-id>
</element-citation>
</ref>
<ref id="CR6"><label>6.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Frei</surname>
<given-names>K</given-names>
</name>
<name><surname>Ramsebner</surname>
<given-names>R</given-names>
</name>
<name><surname>Lucas</surname>
<given-names>T</given-names>
</name>
<name><surname>Hamader</surname>
<given-names>G</given-names>
</name>
<name><surname>Szuhai</surname>
<given-names>K</given-names>
</name>
<name><surname>Weipoltshammer</surname>
<given-names>K</given-names>
</name>
<etal></etal>
</person-group>
<article-title><italic>GJB2</italic>
mutations in hearing impairment: identification of a broad clinical spectrum for improved genetic counseling</article-title>
<source>Laryngoscope</source>
<year>2005</year>
<volume>115</volume>
<fpage>461</fpage>
<lpage>465</lpage>
<pub-id pub-id-type="doi">10.1097/01.mlg.0000157855.47143.71</pub-id>
<pub-id pub-id-type="pmid">15744158</pub-id>
</element-citation>
</ref>
<ref id="CR7"><label>7.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ammar-Khodja</surname>
<given-names>F</given-names>
</name>
<name><surname>Makrelouf</surname>
<given-names>M</given-names>
</name>
<name><surname>Malek</surname>
<given-names>R</given-names>
</name>
<name><surname>Ibrahim</surname>
<given-names>H</given-names>
</name>
<name><surname>Zenati</surname>
<given-names>A</given-names>
</name>
</person-group>
<article-title>Frequency of the 35 delG allele causing non-syndromic recessive deafness in the Algerian patients</article-title>
<source>Genet Couns</source>
<year>2007</year>
<volume>18</volume>
<fpage>383</fpage>
<lpage>391</lpage>
<pub-id pub-id-type="pmid">18286819</pub-id>
</element-citation>
</ref>
<ref id="CR8"><label>8.</label>
<mixed-citation publication-type="other">Ammar-Khodja F, Bonnet C, Dahmani M, Ouhab S, Lefèvre GM, Ibrahim H, et al. Diversity of the causal genes in hearing impaired Algerian individuals identified by whole exome sequencing. Mol Genet Genom Med 2015;3:189-96.</mixed-citation>
</ref>
<ref id="CR9"><label>9.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Delmaghani</surname>
<given-names>S</given-names>
</name>
<name><surname>Aghaie</surname>
<given-names>A</given-names>
</name>
<name><surname>Michalski</surname>
<given-names>N</given-names>
</name>
<name><surname>Bonnet</surname>
<given-names>C</given-names>
</name>
<name><surname>Weil</surname>
<given-names>D</given-names>
</name>
<name><surname>Petit</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR causes DFNB98 profound deafness</article-title>
<source>Hum Mol Genet</source>
<year>2012</year>
<volume>21</volume>
<fpage>3835</fpage>
<lpage>3844</lpage>
<pub-id pub-id-type="doi">10.1093/hmg/dds212</pub-id>
<pub-id pub-id-type="pmid">22678063</pub-id>
</element-citation>
</ref>
<ref id="CR10"><label>10.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>del Castillo</surname>
<given-names>FJ</given-names>
</name>
<name><surname>Rodriguez‐Ballesteros</surname>
<given-names>M</given-names>
</name>
<name><surname>Alvarez</surname>
<given-names>A</given-names>
</name>
<name><surname>Hutchin</surname>
<given-names>T</given-names>
</name>
<name><surname>Leonardi</surname>
<given-names>E</given-names>
</name>
<name><surname>de Oliveira</surname>
<given-names>CA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A novel deletion involving the connexin‐30 gene, del(GJB6‐d13s1854), found in trans with mutations in the <italic>GJB2</italic>
gene (connexin‐26) in subjects with DFNB1 non‐syndromic hearing impairment</article-title>
<source>J Med Genet</source>
<year>2005</year>
<volume>42</volume>
<fpage>588</fpage>
<lpage>594</lpage>
<pub-id pub-id-type="doi">10.1136/jmg.2004.028324</pub-id>
<pub-id pub-id-type="pmid">15994881</pub-id>
</element-citation>
</ref>
<ref id="CR11"><label>11.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Furness</surname>
<given-names>DN</given-names>
</name>
<name><surname>Johnson</surname>
<given-names>SL</given-names>
</name>
<name><surname>Manor</surname>
<given-names>U</given-names>
</name>
<name><surname>Ruttiger</surname>
<given-names>L</given-names>
</name>
<name><surname>Tocchetti</surname>
<given-names>A</given-names>
</name>
<name><surname>Offenhauser</surname>
<given-names>N</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2</article-title>
<source>Proc Natl Acad Sci U S A</source>
<year>2013</year>
<volume>110</volume>
<fpage>13898</fpage>
<lpage>13903</lpage>
<pub-id pub-id-type="doi">10.1073/pnas.1304644110</pub-id>
<pub-id pub-id-type="pmid">23918390</pub-id>
</element-citation>
</ref>
<ref id="CR12"><label>12.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abe</surname>
<given-names>S</given-names>
</name>
<name><surname>Usami</surname>
<given-names>S</given-names>
</name>
<name><surname>Hoover</surname>
<given-names>DM</given-names>
</name>
<name><surname>Cohn</surname>
<given-names>E</given-names>
</name>
<name><surname>Shinkawa</surname>
<given-names>H</given-names>
</name>
<name><surname>Kimberling</surname>
<given-names>WJ</given-names>
</name>
</person-group>
<article-title>Fluctuating sensorineural hearing loss associated with enlarged vestibular aqueduct maps to 7q31, the region containing the Pendred syndrome gene</article-title>
<source>Am J Med Genet</source>
<year>1999</year>
<volume>82</volume>
<fpage>322</fpage>
<lpage>328</lpage>
<pub-id pub-id-type="doi">10.1002/(SICI)1096-8628(19990212)82:4<322::AID-AJMG9>3.0.CO;2-0</pub-id>
<pub-id pub-id-type="pmid">10051166</pub-id>
</element-citation>
</ref>
<ref id="CR13"><label>13.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bladwin</surname>
<given-names>CT</given-names>
</name>
<name><surname>Weiss</surname>
<given-names>S</given-names>
</name>
<name><surname>Farrer</surname>
<given-names>LA</given-names>
</name>
<name><surname>De Stefano</surname>
<given-names>AL</given-names>
</name>
<name><surname>Adair</surname>
<given-names>R</given-names>
</name>
<name><surname>Franklyn</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Linkage of congenital, recessive deafness (DFNB4) to chromosome 7q31 and evidence for genetic heterogeneity in the Middle Eastern Druze population</article-title>
<source>Hum Mol Genet</source>
<year>1995</year>
<volume>4</volume>
<fpage>1637</fpage>
<lpage>1642</lpage>
<pub-id pub-id-type="doi">10.1093/hmg/4.9.1637</pub-id>
<pub-id pub-id-type="pmid">8541853</pub-id>
</element-citation>
</ref>
<ref id="CR14"><label>14.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walsh</surname>
<given-names>T</given-names>
</name>
<name><surname>Walsh</surname>
<given-names>V</given-names>
</name>
<name><surname>Vreugde</surname>
<given-names>S</given-names>
</name>
<name><surname>Hertzano</surname>
<given-names>R</given-names>
</name>
<name><surname>Shahin</surname>
<given-names>H</given-names>
</name>
<name><surname>Haika</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>From flies' eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30</article-title>
<source>Proc Natl Acad Sci U S A</source>
<year>2002</year>
<volume>99</volume>
<fpage>7518</fpage>
<lpage>7523</lpage>
<pub-id pub-id-type="doi">10.1073/pnas.102091699</pub-id>
<pub-id pub-id-type="pmid">12032315</pub-id>
</element-citation>
</ref>
<ref id="CR15"><label>15.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Grillet</surname>
<given-names>N</given-names>
</name>
<name><surname>Schwander</surname>
<given-names>M</given-names>
</name>
<name><surname>Hildebrand</surname>
<given-names>MS</given-names>
</name>
<name><surname>Sczaniecka</surname>
<given-names>A</given-names>
</name>
<name><surname>Kolatkar</surname>
<given-names>A</given-names>
</name>
<name><surname>Velasco</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans</article-title>
<source>Am J Hum Genet</source>
<year>2009</year>
<volume>85</volume>
<fpage>328</fpage>
<lpage>337</lpage>
<pub-id pub-id-type="doi">10.1016/j.ajhg.2009.07.017</pub-id>
<pub-id pub-id-type="pmid">19732867</pub-id>
</element-citation>
</ref>
<ref id="CR16"><label>16.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Delmaghani</surname>
<given-names>S</given-names>
</name>
<name><surname>del Castillo</surname>
<given-names>FG</given-names>
</name>
<name><surname>Michel</surname>
<given-names>V</given-names>
</name>
<name><surname>Leibovici</surname>
<given-names>M</given-names>
</name>
<name><surname>Aghaie</surname>
<given-names>A</given-names>
</name>
<name><surname>Ron</surname>
<given-names>U</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy</article-title>
<source>Nat Genet</source>
<year>2006</year>
<volume>38</volume>
<fpage>770</fpage>
<lpage>778</lpage>
<pub-id pub-id-type="doi">10.1038/ng1829</pub-id>
<pub-id pub-id-type="pmid">16804542</pub-id>
</element-citation>
</ref>
<ref id="CR17"><label>17.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwander</surname>
<given-names>M</given-names>
</name>
<name><surname>Sczaniecka</surname>
<given-names>A</given-names>
</name>
<name><surname>Grillet</surname>
<given-names>N</given-names>
</name>
<name><surname>Bailey</surname>
<given-names>JS</given-names>
</name>
<name><surname>Avenarius</surname>
<given-names>M</given-names>
</name>
<name><surname>Najmabadi</surname>
<given-names>H</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A forward genetics screen in mice identifies recessive deafness traits and reveals that pejvakin is essential for outer hair cell function</article-title>
<source>J Neurosci</source>
<year>2007</year>
<volume>27</volume>
<fpage>2163</fpage>
<lpage>2175</lpage>
<pub-id pub-id-type="doi">10.1523/JNEUROSCI.4975-06.2007</pub-id>
<pub-id pub-id-type="pmid">17329413</pub-id>
</element-citation>
</ref>
<ref id="CR18"><label>18.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ebermann</surname>
<given-names>I</given-names>
</name>
<name><surname>Walger</surname>
<given-names>M</given-names>
</name>
<name><surname>Scholl</surname>
<given-names>HPN</given-names>
</name>
<name><surname>Issa</surname>
<given-names>PC</given-names>
</name>
<name><surname>Luke</surname>
<given-names>C</given-names>
</name>
<name><surname>Nurnberg</surname>
<given-names>G</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Truncating mutation of the DFNB59 gene causes cochlear hearing impairment and central vestibular dysfunction</article-title>
<source>Hum Mutat</source>
<year>2007</year>
<volume>28</volume>
<fpage>571</fpage>
<lpage>577</lpage>
<pub-id pub-id-type="doi">10.1002/humu.20478</pub-id>
<pub-id pub-id-type="pmid">17301963</pub-id>
</element-citation>
</ref>
<ref id="CR19"><label>19.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaleshtori</surname>
<given-names>MH</given-names>
</name>
<name><surname>Simpson</surname>
<given-names>MA</given-names>
</name>
<name><surname>Farrokhi</surname>
<given-names>E</given-names>
</name>
<name><surname>Dolati</surname>
<given-names>M</given-names>
</name>
<name><surname>Rad</surname>
<given-names>LH</given-names>
</name>
<name><surname>Geshnigani</surname>
<given-names>SA</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Novel mutations in the pejvakin gene are associated with autosomal recessive non-syndromic hearing loss in Iranian families</article-title>
<source>Clin Genet</source>
<year>2007</year>
<volume>72</volume>
<fpage>261</fpage>
<lpage>263</lpage>
<pub-id pub-id-type="doi">10.1111/j.1399-0004.2007.00852.x</pub-id>
<pub-id pub-id-type="pmid">17718865</pub-id>
</element-citation>
</ref>
<ref id="CR20"><label>20.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Collin</surname>
<given-names>RWJ</given-names>
</name>
<name><surname>Kalay</surname>
<given-names>E</given-names>
</name>
<name><surname>Oostrik</surname>
<given-names>J</given-names>
</name>
<name><surname>Caylan</surname>
<given-names>R</given-names>
</name>
<name><surname>Wollnik</surname>
<given-names>B</given-names>
</name>
<name><surname>Arslan</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Involvement of DFNB59 mutations in autosomal recessive nonsyndromic hearing impairment</article-title>
<source>Hum Mutat</source>
<year>2007</year>
<volume>28</volume>
<fpage>718</fpage>
<lpage>723</lpage>
<pub-id pub-id-type="doi">10.1002/humu.20510</pub-id>
<pub-id pub-id-type="pmid">17373699</pub-id>
</element-citation>
</ref>
<ref id="CR21"><label>21.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname>
<given-names>M</given-names>
</name>
<name><surname>Duman</surname>
<given-names>D</given-names>
</name>
<name><surname>Cengiz</surname>
<given-names>FB</given-names>
</name>
<name><surname>Bademci</surname>
<given-names>G</given-names>
</name>
<name><surname>Tokgöz-Yilmaz</surname>
<given-names>S</given-names>
</name>
<name><surname>Hişmi</surname>
<given-names>B</given-names>
</name>
<etal></etal>
</person-group>
<article-title>A truncating mutation in <italic>SERPINB6</italic>
is associated with autosomal recessive nonsyndromic sensorineural hearing loss</article-title>
<source>Am J Hum Genet</source>
<year>2010</year>
<volume>86</volume>
<fpage>797</fpage>
<lpage>804</lpage>
<pub-id pub-id-type="doi">10.1016/j.ajhg.2010.04.004</pub-id>
<pub-id pub-id-type="pmid">20451170</pub-id>
</element-citation>
</ref>
<ref id="CR22"><label>22.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rehman</surname>
<given-names>AU</given-names>
</name>
<name><surname>Morell</surname>
<given-names>RJ</given-names>
</name>
<name><surname>Belyantseva</surname>
<given-names>IA</given-names>
</name>
<name><surname>Khan</surname>
<given-names>SY</given-names>
</name>
<name><surname>Boger</surname>
<given-names>ET</given-names>
</name>
<name><surname>Shahzad</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Targeted capture and next-generation sequencing identifies <italic>C9orf75</italic>
, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79</article-title>
<source>Am J Hum Genet</source>
<year>2010</year>
<volume>86</volume>
<fpage>378</fpage>
<lpage>388</lpage>
<pub-id pub-id-type="doi">10.1016/j.ajhg.2010.01.030</pub-id>
<pub-id pub-id-type="pmid">20170899</pub-id>
</element-citation>
</ref>
<ref id="CR23"><label>23.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname>
<given-names>Y</given-names>
</name>
<name><surname>Pohl</surname>
<given-names>E</given-names>
</name>
<name><surname>Boulouiz</surname>
<given-names>R</given-names>
</name>
<name><surname>Schraders</surname>
<given-names>M</given-names>
</name>
<name><surname>Nurnberg</surname>
<given-names>G</given-names>
</name>
<name><surname>Charif</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Mutations in <italic>TPRN</italic>
cause a progressive form of autosomal-recessive nonsyndromic hearing loss</article-title>
<source>Am J Hum Genet</source>
<year>2010</year>
<volume>86</volume>
<fpage>479</fpage>
<lpage>484</lpage>
<pub-id pub-id-type="doi">10.1016/j.ajhg.2010.02.003</pub-id>
<pub-id pub-id-type="pmid">20170898</pub-id>
</element-citation>
</ref>
<ref id="CR24"><label>24.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Veske</surname>
<given-names>A</given-names>
</name>
<name><surname>Oehlmann</surname>
<given-names>R</given-names>
</name>
<name><surname>Younus</surname>
<given-names>F</given-names>
</name>
<name><surname>Mohyuddin</surname>
<given-names>A</given-names>
</name>
<name><surname>Müller-Myhsok</surname>
<given-names>B</given-names>
</name>
<name><surname>Qasim Mehdi</surname>
<given-names>S</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Autosomal recessive non-syndromic deafness locus (DFNB8) maps on chromosome 21q22 in a large consanguineous kindred from Pakistan</article-title>
<source>Hum Mol Genet</source>
<year>1996</year>
<volume>5</volume>
<fpage>165</fpage>
<lpage>168</lpage>
<pub-id pub-id-type="doi">10.1093/hmg/5.1.165</pub-id>
<pub-id pub-id-type="pmid">8789456</pub-id>
</element-citation>
</ref>
<ref id="CR25"><label>25.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Scott</surname>
<given-names>HS</given-names>
</name>
<name><surname>Kudoh</surname>
<given-names>J</given-names>
</name>
<name><surname>Wattenhofer</surname>
<given-names>M</given-names>
</name>
<name><surname>Shibuya</surname>
<given-names>K</given-names>
</name>
<name><surname>Berry</surname>
<given-names>A</given-names>
</name>
<name><surname>Chrast</surname>
<given-names>R</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness</article-title>
<source>Nat Genet</source>
<year>2001</year>
<volume>27</volume>
<fpage>59</fpage>
<lpage>63</lpage>
<pub-id pub-id-type="pmid">11137999</pub-id>
</element-citation>
</ref>
<ref id="CR26"><label>26.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Charizopoulou</surname>
<given-names>N</given-names>
</name>
<name><surname>Lelli</surname>
<given-names>A</given-names>
</name>
<name><surname>Schraders</surname>
<given-names>M</given-names>
</name>
<name><surname>Ray</surname>
<given-names>K</given-names>
</name>
<name><surname>Hildebrand</surname>
<given-names>MS</given-names>
</name>
<name><surname>Ramesh</surname>
<given-names>A</given-names>
</name>
<etal></etal>
</person-group>
<article-title><italic>Gipc3</italic>
mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human</article-title>
<source>Nat Commun</source>
<year>2011</year>
<volume>2</volume>
<fpage>201</fpage>
<lpage>212</lpage>
<pub-id pub-id-type="doi">10.1038/ncomms1200</pub-id>
<pub-id pub-id-type="pmid">21326233</pub-id>
</element-citation>
</ref>
<ref id="CR27"><label>27.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Horn</surname>
<given-names>HF</given-names>
</name>
<name><surname>Brownstein</surname>
<given-names>Z</given-names>
</name>
<name><surname>Lenz</surname>
<given-names>DR</given-names>
</name>
<name><surname>Shivatzki</surname>
<given-names>S</given-names>
</name>
<name><surname>Dror</surname>
<given-names>AA</given-names>
</name>
<name><surname>Dagan-Rosenfeld</surname>
<given-names>O</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The LINC complex is essential for hearing</article-title>
<source>J Clin Invest</source>
<year>2013</year>
<volume>123</volume>
<fpage>740</fpage>
<lpage>750</lpage>
<pub-id pub-id-type="pmid">23348741</pub-id>
</element-citation>
</ref>
<ref id="CR28"><label>28.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Imtiaz</surname>
<given-names>A</given-names>
</name>
<name><surname>Kohrman</surname>
<given-names>DC</given-names>
</name>
<name><surname>Naz</surname>
<given-names>SA</given-names>
</name>
</person-group>
<article-title>Frameshift mutation in <italic>GRXCR2</italic>
causes recessively inherited hearing loss</article-title>
<source>Hum Mutat</source>
<year>2014</year>
<volume>35</volume>
<fpage>618</fpage>
<lpage>624</lpage>
<pub-id pub-id-type="doi">10.1002/humu.22545</pub-id>
<pub-id pub-id-type="pmid">24619944</pub-id>
</element-citation>
</ref>
<ref id="CR29"><label>29.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seco</surname>
<given-names>CZ</given-names>
</name>
<name><surname>Oonk</surname>
<given-names>AM</given-names>
</name>
<name><surname>Domınguez-Ruiz</surname>
<given-names>M</given-names>
</name>
<name><surname>Draaisma</surname>
<given-names>JMT</given-names>
</name>
<name><surname>Gandi</surname>
<given-names>M</given-names>
</name>
<name><surname>Oostrik</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in <italic>CLIC5</italic>
</article-title>
<source>Eur J Hum Genet</source>
<year>2014</year>
<volume>23</volume>
<fpage>189</fpage>
<lpage>194</lpage>
<pub-id pub-id-type="doi">10.1038/ejhg.2014.83</pub-id>
<pub-id pub-id-type="pmid">24781754</pub-id>
</element-citation>
</ref>
<ref id="CR30"><label>30.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Heer</surname>
<given-names>AM</given-names>
</name>
<name><surname>Collin</surname>
<given-names>RW</given-names>
</name>
<name><surname>Huygen</surname>
<given-names>PL</given-names>
</name>
<name><surname>Schraders</surname>
<given-names>M</given-names>
</name>
<name><surname>Oostrik</surname>
<given-names>J</given-names>
</name>
<name><surname>Rouwette</surname>
<given-names>M</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Progressive sensorineural hearing loss and normal vestibular function in a Dutch DFNB7/11 family with a novel mutation in <italic>TMC1</italic>
</article-title>
<source>Audiol Neurootol</source>
<year>2011</year>
<volume>16</volume>
<fpage>93</fpage>
<lpage>105</lpage>
<pub-id pub-id-type="doi">10.1159/000313282</pub-id>
<pub-id pub-id-type="pmid">21252500</pub-id>
</element-citation>
</ref>
<ref id="CR31"><label>31.</label>
<mixed-citation publication-type="other">Mori K, Miyanohara I, Moteki H, Nishio SY, Kurono Y, Usami SI. Novel Mutations in <italic>GRXCR1</italic>
at DFNB25 lead to progressive hearing loss and dizziness. Ann Otol Rhinol Laryngol. 2015;0003489415575061.</mixed-citation>
</ref>
<ref id="CR32"><label>32.</label>
<mixed-citation publication-type="other">Ichinose A, Moteki H, Hattori M, Nishio SY, Usami SI. Novel mutations in <italic>LRTOMT</italic>
associated with moderate progressive hearing loss in autosomal recessive inheritance. Ann Otol Rhinol Laryngol. 2015;0003489415575043.</mixed-citation>
</ref>
<ref id="CR33"><label>33.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Offenhäuser</surname>
<given-names>N</given-names>
</name>
<name><surname>Borgonovo</surname>
<given-names>A</given-names>
</name>
<name><surname>Disanza</surname>
<given-names>A</given-names>
</name>
<name><surname>Romano</surname>
<given-names>P</given-names>
</name>
<name><surname>Ponzanelli</surname>
<given-names>I</given-names>
</name>
<name><surname>Iannolo</surname>
<given-names>G</given-names>
</name>
<etal></etal>
</person-group>
<article-title>The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway</article-title>
<source>Mol Biol Cell</source>
<year>2004</year>
<volume>15</volume>
<fpage>91</fpage>
<lpage>98</lpage>
<pub-id pub-id-type="doi">10.1091/mbc.E03-06-0427</pub-id>
<pub-id pub-id-type="pmid">14565974</pub-id>
</element-citation>
</ref>
<ref id="CR34"><label>34.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zampini</surname>
<given-names>V</given-names>
</name>
<name><surname>Ruttiger</surname>
<given-names>L</given-names>
</name>
<name><surname>Johnson</surname>
<given-names>SL</given-names>
</name>
<name><surname>Franz</surname>
<given-names>C</given-names>
</name>
<name><surname>Furness</surname>
<given-names>DN</given-names>
</name>
<name><surname>Waldhaus</surname>
<given-names>J</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Eps8 regulates hair bundle length and functional maturation of mammalian auditory hair cells</article-title>
<source>PLoS Biol</source>
<year>2011</year>
<volume>9</volume>
<pub-id pub-id-type="doi">10.1371/journal.pbio.1001048</pub-id>
<pub-id pub-id-type="pmid">21526224</pub-id>
</element-citation>
</ref>
<ref id="CR35"><label>35.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Behlouli</surname>
<given-names>A</given-names>
</name>
<name><surname>Bonnet</surname>
<given-names>C</given-names>
</name>
<name><surname>Abdi</surname>
<given-names>S</given-names>
</name>
<name><surname>Bouaita</surname>
<given-names>A</given-names>
</name>
<name><surname>Lelli</surname>
<given-names>A</given-names>
</name>
<name><surname>Hardelin</surname>
<given-names>J-P</given-names>
</name>
<etal></etal>
</person-group>
<article-title><italic>EPS8</italic>
, encoding an actin-binding protein of cochlear hair cell stereocilia, is a new causal gene for autosomal recessive profound deafness</article-title>
<source>Orph J Rar Dis</source>
<year>2014</year>
<volume>9</volume>
<fpage>55</fpage>
<pub-id pub-id-type="doi">10.1186/1750-1172-9-55</pub-id>
</element-citation>
</ref>
<ref id="CR36"><label>36.</label>
<element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Manor</surname>
<given-names>U</given-names>
</name>
<name><surname>Disanza</surname>
<given-names>A</given-names>
</name>
<name><surname>Grati</surname>
<given-names>MH</given-names>
</name>
<name><surname>Andrade</surname>
<given-names>L</given-names>
</name>
<name><surname>Lin</surname>
<given-names>H</given-names>
</name>
<name><surname>Di Fiore</surname>
<given-names>PP</given-names>
</name>
<etal></etal>
</person-group>
<article-title>Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8</article-title>
<source>Curr Biol</source>
<year>2011</year>
<volume>21</volume>
<fpage>167</fpage>
<lpage>172</lpage>
<pub-id pub-id-type="doi">10.1016/j.cub.2010.12.046</pub-id>
<pub-id pub-id-type="pmid">21236676</pub-id>
</element-citation>
</ref>
</ref-list>
</back>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/MaghrebDataLibMedV2/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 0000709 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 0000709 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= MaghrebDataLibMedV2 |flux= Pmc |étape= Corpus |type= RBID |clé= |texte= }}
![]() | This area was generated with Dilib version V0.6.38. | ![]() |