SCNIA duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis
Identifieur interne : 008107 ( Main/Exploration ); précédent : 008106; suivant : 008108SCNIA duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis
Auteurs : Carla Marini [Italie] ; Ingrid E. Scheffer [Australie] ; Rima Nabbout [France] ; Divide Mei [Italie] ; Kathy Cox [Australie] ; Leanne M. Dibbens [Australie] ; Jacinta M. Mcmahon [Australie] ; Xenia Iona [Australie] ; Rochio Sanchez Carpintero [Espagne] ; Maurizio Elia [Italie] ; Maria Roberta Cilio [Italie] ; Nicola Specchio [Italie] ; Lucio Giordano [Italie] ; Pasquale Striano [Italie] ; Elena Gennaro [Italie] ; J. Helen Cross [Royaume-Uni] ; Sara Kivity [Israël] ; Miriam Y. Neufeld [Israël] ; Zaid Afawi [Israël] ; Eva Andermann [Canada] ; Daniel Keene [Canada] ; Olivier Dulac [France] ; Federico Zara [Italie] ; Samuel F. Berkovic [Australie] ; Renzo Guerrini [Italie] ; John C. Mulley [Australie]Source :
- Epilepsia : (Copenhagen) [ 0013-9580 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Objective: We aimed to determine the type, frequency, and size of microchromosomal copy number variations (CNVs) affecting the neuronal sodium channel α I subunit gene (SCNIA) in Dravet syndrome (DS), other epileptic encephalopathies, and generalized epilepsy with febrile seizures plus (GEFS+). Methods: Multiplex ligation-dependent probe amplification (MLPA) was applied to detect SCNIA CNVs among 289 cases (I26 DS, 97 GEFS+, and 66 with other phenotypes). CNVs extending beyond SCNIA were further characterized by comparative genome hybridization (array CGH). Results: Novel SCNIA CNVs were found in I2.5% of DS patients where sequence-based mutations had been excluded. We identified the first partial SCNIA duplications in two siblings with typical DS and in a patient with early-onset symptomatic generalized epilepsy. In addition, a patient with DS had a partial SCNIA amplification of 5-6 copies. The remaining CNVs abnormalities were four partial and nine whole SCNIA deletions involving contiguous genes. Two CNVs (a partial SCNIA deletion and a duplication) were inherited from a parent, in whom there was mosaicism. Array CGH showed intragenic deletions of 90 kb and larger, with the largest of 9.3 Mb deleting 49 contiguous genes and extending beyond SCNIA. Discussion: Duplication and amplification involving SCNIA are now added to molecular mechanisms of DS patients. Our findings showed that 12.5% of DS patients who are mutation negative have MLPA-detected SCNIA CNVs with an overall frequency of about 2-3%. MLPA is the established second-line testing strategy to reliably detect all CNVs of SCNIA from the megabase range down to one exon. Large CNVs extending outside SCNIA and involving contiguous genes can be precisely characterized by array CGH.
Affiliations:
- Australie, Canada, Espagne, France, Israël, Italie, Royaume-Uni
- Angleterre, Grand Londres, Latium, Québec, Victoria (État), Île-de-France
- Londres, Melbourne, Montréal, Paris, Rome
- Université McGill, Université de Melbourne
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Dibbens</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>School of Pediatrics and Reproductive Health, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>6 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Mcmahon, Jacinta M" sort="Mcmahon, Jacinta M" uniqKey="Mcmahon J" first="Jacinta M." last="Mcmahon">Jacinta M. Mcmahon</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Medicine (Neurology), University of Melbourne and Austin Health</s1><s2>Heidelberg</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg</wicri:noRegion></affiliation></author><author><name sortKey="Iona, Xenia" sort="Iona, Xenia" uniqKey="Iona X" first="Xenia" last="Iona">Xenia Iona</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Sanchez Carpintero, Rochio" sort="Sanchez Carpintero, Rochio" uniqKey="Sanchez Carpintero R" first="Rochio" last="Sanchez Carpintero">Rochio Sanchez Carpintero</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Paediatric Neurology Unit, Department of Paediatrics, Clinica Universitaria de Navarra, University of Navarra</s1><s2>Pamplona</s2><s3>ESP</s3><sZ>9 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>Pamplona</wicri:noRegion></affiliation></author><author><name sortKey="Elia, Maurizio" sort="Elia, Maurizio" uniqKey="Elia M" first="Maurizio" last="Elia">Maurizio Elia</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS)</s1><s2>Troina, Enna</s2><s3>ITA</s3><sZ>10 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Troina, Enna</wicri:noRegion></affiliation></author><author><name sortKey="Cilio, Maria Roberta" sort="Cilio, Maria Roberta" uniqKey="Cilio M" first="Maria Roberta" last="Cilio">Maria Roberta Cilio</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Division of Neurology, Bambino Gesu Children's Hospital</s1><s2>Roma</s2><s3>ITA</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Specchio, Nicola" sort="Specchio, Nicola" uniqKey="Specchio N" first="Nicola" last="Specchio">Nicola Specchio</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Division of Neurology, Bambino Gesu Children's Hospital</s1><s2>Roma</s2><s3>ITA</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Giordano, Lucio" sort="Giordano, Lucio" uniqKey="Giordano L" first="Lucio" last="Giordano">Lucio Giordano</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Child and Adolescent Neurology and Psychiatry, Spedali Civili</s1><s2>Brescia</s2><s3>ITA</s3><sZ>13 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Brescia</wicri:noRegion></affiliation></author><author><name sortKey="Striano, Pasquale" sort="Striano, Pasquale" uniqKey="Striano P" first="Pasquale" last="Striano">Pasquale Striano</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, University of Genova</s1><s2>Genova</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Gennaro, Elena" sort="Gennaro, Elena" uniqKey="Gennaro E" first="Elena" last="Gennaro">Elena Gennaro</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Laboratory of Genetics, E.O. Ospedale Galliera</s1><s2>Genova</s2><s3>ITA</s3><sZ>15 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Cross, J Helen" sort="Cross, J Helen" uniqKey="Cross J" first="J. Helen" last="Cross">J. Helen Cross</name><affiliation wicri:level="3"><inist:fA14 i1="13"><s1>UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust</s1><s2>London</s2><s3>GBR</s3><sZ>16 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Kivity, Sara" sort="Kivity, Sara" uniqKey="Kivity S" first="Sara" last="Kivity">Sara Kivity</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Schneider Children's Medical Center</s1><s2>Petaq Tikva</s2><s3>ISR</s3><sZ>17 aut.</sZ></inist:fA14><country>Israël</country><wicri:noRegion>Schneider Children's Medical Center</wicri:noRegion></affiliation></author><author><name sortKey="Neufeld, Miriam Y" sort="Neufeld, Miriam Y" uniqKey="Neufeld M" first="Miriam Y." last="Neufeld">Miriam Y. Neufeld</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Neurology, Tel Aviv Sourasky Medical Centre</s1><s2>Tel Aviv</s2><s3>ISR</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Israël</country><wicri:noRegion>Tel Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Afawi, Zaid" sort="Afawi, Zaid" uniqKey="Afawi Z" first="Zaid" last="Afawi">Zaid Afawi</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Neurology, Tel Aviv Sourasky Medical Centre</s1><s2>Tel Aviv</s2><s3>ISR</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Israël</country><wicri:noRegion>Tel Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Andermann, Eva" sort="Andermann, Eva" uniqKey="Andermann E" first="Eva" last="Andermann">Eva Andermann</name><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University</s1><s2>Montreal</s2><s3>CAN</s3><sZ>20 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region><settlement type="city">Montréal</settlement></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Keene, Daniel" sort="Keene, Daniel" uniqKey="Keene D" first="Daniel" last="Keene">Daniel Keene</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Department of Pediatrics, Children's Hospital of Eastern Ontario</s1><s2>Ottawa, Ontario</s2><s3>CAN</s3><sZ>21 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ottawa, Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Dulac, Olivier" sort="Dulac, Olivier" uniqKey="Dulac O" first="Olivier" last="Dulac">Olivier Dulac</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Service de Neurologie Pédiatrique, AP-HP, Hopital Necker-Enfants Malades, Centre de Référence Épilepsies Rares</s1><s2>Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Zara, Federico" sort="Zara, Federico" uniqKey="Zara F" first="Federico" last="Zara">Federico Zara</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, University of Genova</s1><s2>Genova</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Berkovic, Samuel F" sort="Berkovic, Samuel F" uniqKey="Berkovic S" first="Samuel F." last="Berkovic">Samuel F. Berkovic</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Medicine (Neurology), University of Melbourne and Austin Health</s1><s2>Heidelberg</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg</wicri:noRegion></affiliation></author><author><name sortKey="Guerrini, Renzo" sort="Guerrini, Renzo" uniqKey="Guerrini R" first="Renzo" last="Guerrini">Renzo Guerrini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Child Neurology Unit, Children's Hospital A. Meyer, University of Florence</s1><s2>Florence</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Mulley, John C" sort="Mulley, John C" uniqKey="Mulley J" first="John C." last="Mulley">John C. Mulley</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>School of Pediatrics and Reproductive Health, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>6 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>School of Molecular and Biomedical Sciences, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0308727</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0308727 INIST</idno><idno type="RBID">Pascal:09-0308727</idno><idno type="wicri:Area/PascalFrancis/Corpus">002D09</idno><idno type="wicri:Area/PascalFrancis/Curation">003311</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">002864</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">002864</idno><idno type="wicri:doubleKey">0013-9580:2009:Marini C:scnia:duplications:and</idno><idno type="wicri:Area/Main/Merge">008833</idno><idno type="wicri:Area/Main/Curation">008107</idno><idno type="wicri:Area/Main/Exploration">008107</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">SCNIA duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis</title><author><name sortKey="Marini, Carla" sort="Marini, Carla" uniqKey="Marini C" first="Carla" last="Marini">Carla Marini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Child Neurology Unit, Children's Hospital A. Meyer, University of Florence</s1><s2>Florence</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Scheffer, Ingrid E" sort="Scheffer, Ingrid E" uniqKey="Scheffer I" first="Ingrid E." last="Scheffer">Ingrid E. Scheffer</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Medicine (Neurology), University of Melbourne and Austin Health</s1><s2>Heidelberg</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Paediatrics, University of Melbourne, Royal Children's Hospital</s1><s2>Melbourne</s2><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Nabbout, Rima" sort="Nabbout, Rima" uniqKey="Nabbout R" first="Rima" last="Nabbout">Rima Nabbout</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Service de Neurologie Pédiatrique, AP-HP, Hopital Necker-Enfants Malades, Centre de Référence Épilepsies Rares</s1><s2>Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mei, Divide" sort="Mei, Divide" uniqKey="Mei D" first="Divide" last="Mei">Divide Mei</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Child Neurology Unit, Children's Hospital A. Meyer, University of Florence</s1><s2>Florence</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Cox, Kathy" sort="Cox, Kathy" uniqKey="Cox K" first="Kathy" last="Cox">Kathy Cox</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Dibbens, Leanne M" sort="Dibbens, Leanne M" uniqKey="Dibbens L" first="Leanne M." last="Dibbens">Leanne M. Dibbens</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>School of Pediatrics and Reproductive Health, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>6 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Mcmahon, Jacinta M" sort="Mcmahon, Jacinta M" uniqKey="Mcmahon J" first="Jacinta M." last="Mcmahon">Jacinta M. Mcmahon</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Medicine (Neurology), University of Melbourne and Austin Health</s1><s2>Heidelberg</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg</wicri:noRegion></affiliation></author><author><name sortKey="Iona, Xenia" sort="Iona, Xenia" uniqKey="Iona X" first="Xenia" last="Iona">Xenia Iona</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Sanchez Carpintero, Rochio" sort="Sanchez Carpintero, Rochio" uniqKey="Sanchez Carpintero R" first="Rochio" last="Sanchez Carpintero">Rochio Sanchez Carpintero</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Paediatric Neurology Unit, Department of Paediatrics, Clinica Universitaria de Navarra, University of Navarra</s1><s2>Pamplona</s2><s3>ESP</s3><sZ>9 aut.</sZ></inist:fA14><country>Espagne</country><wicri:noRegion>Pamplona</wicri:noRegion></affiliation></author><author><name sortKey="Elia, Maurizio" sort="Elia, Maurizio" uniqKey="Elia M" first="Maurizio" last="Elia">Maurizio Elia</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology, Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS)</s1><s2>Troina, Enna</s2><s3>ITA</s3><sZ>10 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Troina, Enna</wicri:noRegion></affiliation></author><author><name sortKey="Cilio, Maria Roberta" sort="Cilio, Maria Roberta" uniqKey="Cilio M" first="Maria Roberta" last="Cilio">Maria Roberta Cilio</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Division of Neurology, Bambino Gesu Children's Hospital</s1><s2>Roma</s2><s3>ITA</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Specchio, Nicola" sort="Specchio, Nicola" uniqKey="Specchio N" first="Nicola" last="Specchio">Nicola Specchio</name><affiliation wicri:level="3"><inist:fA14 i1="09"><s1>Division of Neurology, Bambino Gesu Children's Hospital</s1><s2>Roma</s2><s3>ITA</s3><sZ>11 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Giordano, Lucio" sort="Giordano, Lucio" uniqKey="Giordano L" first="Lucio" last="Giordano">Lucio Giordano</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Department of Child and Adolescent Neurology and Psychiatry, Spedali Civili</s1><s2>Brescia</s2><s3>ITA</s3><sZ>13 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Brescia</wicri:noRegion></affiliation></author><author><name sortKey="Striano, Pasquale" sort="Striano, Pasquale" uniqKey="Striano P" first="Pasquale" last="Striano">Pasquale Striano</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, University of Genova</s1><s2>Genova</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Gennaro, Elena" sort="Gennaro, Elena" uniqKey="Gennaro E" first="Elena" last="Gennaro">Elena Gennaro</name><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Laboratory of Genetics, E.O. Ospedale Galliera</s1><s2>Genova</s2><s3>ITA</s3><sZ>15 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Cross, J Helen" sort="Cross, J Helen" uniqKey="Cross J" first="J. Helen" last="Cross">J. Helen Cross</name><affiliation wicri:level="3"><inist:fA14 i1="13"><s1>UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust</s1><s2>London</s2><s3>GBR</s3><sZ>16 aut.</sZ></inist:fA14><country>Royaume-Uni</country><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Kivity, Sara" sort="Kivity, Sara" uniqKey="Kivity S" first="Sara" last="Kivity">Sara Kivity</name><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Schneider Children's Medical Center</s1><s2>Petaq Tikva</s2><s3>ISR</s3><sZ>17 aut.</sZ></inist:fA14><country>Israël</country><wicri:noRegion>Schneider Children's Medical Center</wicri:noRegion></affiliation></author><author><name sortKey="Neufeld, Miriam Y" sort="Neufeld, Miriam Y" uniqKey="Neufeld M" first="Miriam Y." last="Neufeld">Miriam Y. Neufeld</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Neurology, Tel Aviv Sourasky Medical Centre</s1><s2>Tel Aviv</s2><s3>ISR</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Israël</country><wicri:noRegion>Tel Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Afawi, Zaid" sort="Afawi, Zaid" uniqKey="Afawi Z" first="Zaid" last="Afawi">Zaid Afawi</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Neurology, Tel Aviv Sourasky Medical Centre</s1><s2>Tel Aviv</s2><s3>ISR</s3><sZ>18 aut.</sZ><sZ>19 aut.</sZ></inist:fA14><country>Israël</country><wicri:noRegion>Tel Aviv</wicri:noRegion></affiliation></author><author><name sortKey="Andermann, Eva" sort="Andermann, Eva" uniqKey="Andermann E" first="Eva" last="Andermann">Eva Andermann</name><affiliation wicri:level="4"><inist:fA14 i1="16"><s1>Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University</s1><s2>Montreal</s2><s3>CAN</s3><sZ>20 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region><settlement type="city">Montréal</settlement></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Keene, Daniel" sort="Keene, Daniel" uniqKey="Keene D" first="Daniel" last="Keene">Daniel Keene</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>Department of Pediatrics, Children's Hospital of Eastern Ontario</s1><s2>Ottawa, Ontario</s2><s3>CAN</s3><sZ>21 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ottawa, Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Dulac, Olivier" sort="Dulac, Olivier" uniqKey="Dulac O" first="Olivier" last="Dulac">Olivier Dulac</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Service de Neurologie Pédiatrique, AP-HP, Hopital Necker-Enfants Malades, Centre de Référence Épilepsies Rares</s1><s2>Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>22 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Zara, Federico" sort="Zara, Federico" uniqKey="Zara F" first="Federico" last="Zara">Federico Zara</name><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, University of Genova</s1><s2>Genova</s2><s3>ITA</s3><sZ>14 aut.</sZ><sZ>23 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Berkovic, Samuel F" sort="Berkovic, Samuel F" uniqKey="Berkovic S" first="Samuel F." last="Berkovic">Samuel F. Berkovic</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Medicine (Neurology), University of Melbourne and Austin Health</s1><s2>Heidelberg</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Heidelberg</wicri:noRegion></affiliation></author><author><name sortKey="Guerrini, Renzo" sort="Guerrini, Renzo" uniqKey="Guerrini R" first="Renzo" last="Guerrini">Renzo Guerrini</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Child Neurology Unit, Children's Hospital A. Meyer, University of Florence</s1><s2>Florence</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Florence</wicri:noRegion></affiliation></author><author><name sortKey="Mulley, John C" sort="Mulley, John C" uniqKey="Mulley J" first="John C." last="Mulley">John C. Mulley</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Genetic Medicine, Women's and Children's Hospital</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>School of Pediatrics and Reproductive Health, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>6 aut.</sZ><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>School of Molecular and Biomedical Sciences, University of Adelaide</s1><s2>Adelaide</s2><s3>AUS</s3><sZ>26 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Epilepsia : (Copenhagen)</title><title level="j" type="abbreviated">Epilepsia : (Cph.)</title><idno type="ISSN">0013-9580</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Epilepsia : (Copenhagen)</title><title level="j" type="abbreviated">Epilepsia : (Cph.)</title><idno type="ISSN">0013-9580</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amplification</term><term>Deletion</term><term>Diagnosis</term><term>Dravet syndrome</term><term>Duplication</term><term>Epilepsy</term><term>Nervous system diseases</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Délétion</term><term>Syndrome de Dravet</term><term>Epilepsie</term><term>Pathologie du système nerveux</term><term>Duplication</term><term>Diagnostic</term><term>Amplification</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: We aimed to determine the type, frequency, and size of microchromosomal copy number variations (CNVs) affecting the neuronal sodium channel α I subunit gene (SCNIA) in Dravet syndrome (DS), other epileptic encephalopathies, and generalized epilepsy with febrile seizures plus (GEFS+). Methods: Multiplex ligation-dependent probe amplification (MLPA) was applied to detect SCNIA CNVs among 289 cases (I26 DS, 97 GEFS+, and 66 with other phenotypes). CNVs extending beyond SCNIA were further characterized by comparative genome hybridization (array CGH). Results: Novel SCNIA CNVs were found in I2.5% of DS patients where sequence-based mutations had been excluded. We identified the first partial SCNIA duplications in two siblings with typical DS and in a patient with early-onset symptomatic generalized epilepsy. In addition, a patient with DS had a partial SCNIA amplification of 5-6 copies. The remaining CNVs abnormalities were four partial and nine whole SCNIA deletions involving contiguous genes. Two CNVs (a partial SCNIA deletion and a duplication) were inherited from a parent, in whom there was mosaicism. Array CGH showed intragenic deletions of 90 kb and larger, with the largest of 9.3 Mb deleting 49 contiguous genes and extending beyond SCNIA. Discussion: Duplication and amplification involving SCNIA are now added to molecular mechanisms of DS patients. Our findings showed that 12.5% of DS patients who are mutation negative have MLPA-detected SCNIA CNVs with an overall frequency of about 2-3%. MLPA is the established second-line testing strategy to reliably detect all CNVs of SCNIA from the megabase range down to one exon. Large CNVs extending outside SCNIA and involving contiguous genes can be precisely characterized by array CGH.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>Espagne</li><li>France</li><li>Israël</li><li>Italie</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Latium</li><li>Québec</li><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Londres</li><li>Melbourne</li><li>Montréal</li><li>Paris</li><li>Rome</li></settlement><orgName><li>Université McGill</li><li>Université de Melbourne</li></orgName></list><tree><country name="Italie"><noRegion><name sortKey="Marini, Carla" sort="Marini, Carla" uniqKey="Marini C" first="Carla" last="Marini">Carla Marini</name></noRegion><name sortKey="Cilio, Maria Roberta" sort="Cilio, Maria Roberta" uniqKey="Cilio M" first="Maria Roberta" last="Cilio">Maria Roberta Cilio</name><name sortKey="Elia, Maurizio" sort="Elia, Maurizio" uniqKey="Elia M" first="Maurizio" last="Elia">Maurizio Elia</name><name sortKey="Gennaro, Elena" sort="Gennaro, Elena" uniqKey="Gennaro E" first="Elena" last="Gennaro">Elena Gennaro</name><name sortKey="Giordano, Lucio" sort="Giordano, Lucio" uniqKey="Giordano L" first="Lucio" last="Giordano">Lucio Giordano</name><name sortKey="Guerrini, Renzo" sort="Guerrini, Renzo" uniqKey="Guerrini R" first="Renzo" last="Guerrini">Renzo Guerrini</name><name sortKey="Mei, Divide" sort="Mei, Divide" uniqKey="Mei D" first="Divide" last="Mei">Divide Mei</name><name sortKey="Specchio, Nicola" sort="Specchio, Nicola" uniqKey="Specchio N" first="Nicola" last="Specchio">Nicola Specchio</name><name sortKey="Striano, Pasquale" sort="Striano, Pasquale" uniqKey="Striano P" first="Pasquale" last="Striano">Pasquale Striano</name><name sortKey="Zara, Federico" sort="Zara, Federico" uniqKey="Zara F" first="Federico" last="Zara">Federico Zara</name></country><country name="Australie"><noRegion><name sortKey="Scheffer, Ingrid E" sort="Scheffer, Ingrid E" uniqKey="Scheffer I" first="Ingrid E." last="Scheffer">Ingrid E. Scheffer</name></noRegion><name sortKey="Berkovic, Samuel F" sort="Berkovic, Samuel F" uniqKey="Berkovic S" first="Samuel F." last="Berkovic">Samuel F. Berkovic</name><name sortKey="Cox, Kathy" sort="Cox, Kathy" uniqKey="Cox K" first="Kathy" last="Cox">Kathy Cox</name><name sortKey="Dibbens, Leanne M" sort="Dibbens, Leanne M" uniqKey="Dibbens L" first="Leanne M." last="Dibbens">Leanne M. Dibbens</name><name sortKey="Dibbens, Leanne M" sort="Dibbens, Leanne M" uniqKey="Dibbens L" first="Leanne M." last="Dibbens">Leanne M. Dibbens</name><name sortKey="Iona, Xenia" sort="Iona, Xenia" uniqKey="Iona X" first="Xenia" last="Iona">Xenia Iona</name><name sortKey="Mcmahon, Jacinta M" sort="Mcmahon, Jacinta M" uniqKey="Mcmahon J" first="Jacinta M." last="Mcmahon">Jacinta M. Mcmahon</name><name sortKey="Mulley, John C" sort="Mulley, John C" uniqKey="Mulley J" first="John C." last="Mulley">John C. Mulley</name><name sortKey="Mulley, John C" sort="Mulley, John C" uniqKey="Mulley J" first="John C." last="Mulley">John C. Mulley</name><name sortKey="Mulley, John C" sort="Mulley, John C" uniqKey="Mulley J" first="John C." last="Mulley">John C. Mulley</name><name sortKey="Scheffer, Ingrid E" sort="Scheffer, Ingrid E" uniqKey="Scheffer I" first="Ingrid E." last="Scheffer">Ingrid E. Scheffer</name></country><country name="France"><region name="Île-de-France"><name sortKey="Nabbout, Rima" sort="Nabbout, Rima" uniqKey="Nabbout R" first="Rima" last="Nabbout">Rima Nabbout</name></region><name sortKey="Dulac, Olivier" sort="Dulac, Olivier" uniqKey="Dulac O" first="Olivier" last="Dulac">Olivier Dulac</name></country><country name="Espagne"><noRegion><name sortKey="Sanchez Carpintero, Rochio" sort="Sanchez Carpintero, Rochio" uniqKey="Sanchez Carpintero R" first="Rochio" last="Sanchez Carpintero">Rochio Sanchez Carpintero</name></noRegion></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Cross, J Helen" sort="Cross, J Helen" uniqKey="Cross J" first="J. Helen" last="Cross">J. Helen Cross</name></region></country><country name="Israël"><noRegion><name sortKey="Kivity, Sara" sort="Kivity, Sara" uniqKey="Kivity S" first="Sara" last="Kivity">Sara Kivity</name></noRegion><name sortKey="Afawi, Zaid" sort="Afawi, Zaid" uniqKey="Afawi Z" first="Zaid" last="Afawi">Zaid Afawi</name><name sortKey="Neufeld, Miriam Y" sort="Neufeld, Miriam Y" uniqKey="Neufeld M" first="Miriam Y." last="Neufeld">Miriam Y. Neufeld</name></country><country name="Canada"><region name="Québec"><name sortKey="Andermann, Eva" sort="Andermann, Eva" uniqKey="Andermann E" first="Eva" last="Andermann">Eva Andermann</name></region><name sortKey="Keene, Daniel" sort="Keene, Daniel" uniqKey="Keene D" first="Daniel" last="Keene">Daniel Keene</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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