Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans.
Identifieur interne : 003937 ( PubMed/Corpus ); précédent : 003936; suivant : 003938Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans.
Auteurs : Camille Humbert ; Flora Silbermann ; Bharti Morar ; Mélanie Parisot ; Mohammed Zarhrate ; Cécile Masson ; Frédéric Tores ; Patricia Blanchet ; Marie-José Perez ; Yuliya Petrov ; Philippe Khau Van Kien ; Joelle Roume ; Brigitte Leroy ; Olivier Gribouval ; Luba Kalaydjieva ; Laurence Heidet ; Rémi Salomon ; Corinne Antignac ; Alexandre Benmerah ; Sophie Saunier ; Cécile JeanpierreSource :
- American journal of human genetics [ 1537-6605 ] ; 2014.
English descriptors
- KwdEn :
- Congenital Abnormalities (genetics), Congenital Abnormalities (pathology), Female, Fetus (abnormalities), Genes, Recessive, Homozygote, Humans, Integrin alpha Chains (genetics), Integrin alpha Chains (metabolism), Kidney (abnormalities), Kidney (pathology), Kidney Diseases (congenital), Kidney Diseases (genetics), Kidney Diseases (pathology), Male, Mutation, Pedigree, Urogenital Abnormalities (genetics), Urogenital Abnormalities (pathology).
- MESH :
- chemical , genetics : Integrin alpha Chains.
- abnormalities : Fetus, Kidney.
- congenital : Kidney Diseases.
- genetics : Congenital Abnormalities, Kidney Diseases, Urogenital Abnormalities.
- chemical , metabolism : Integrin alpha Chains.
- pathology : Congenital Abnormalities, Kidney, Kidney Diseases, Urogenital Abnormalities.
- Female, Genes, Recessive, Homozygote, Humans, Male, Mutation, Pedigree.
Abstract
Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease.
DOI: 10.1016/j.ajhg.2013.12.017
PubMed: 24439109
Links to Exploration step
pubmed:24439109Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans.</title><author><name sortKey="Humbert, Camille" sort="Humbert, Camille" uniqKey="Humbert C" first="Camille" last="Humbert">Camille Humbert</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Silbermann, Flora" sort="Silbermann, Flora" uniqKey="Silbermann F" first="Flora" last="Silbermann">Flora Silbermann</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Morar, Bharti" sort="Morar, Bharti" uniqKey="Morar B" first="Bharti" last="Morar">Bharti Morar</name><affiliation><nlm:affiliation>Harry Perkins Institute of Medical Research/Centre for Medical Research, The University of Western Australia, Perth, Nedlands, WA 6009, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Parisot, Melanie" sort="Parisot, Melanie" uniqKey="Parisot M" first="Mélanie" last="Parisot">Mélanie Parisot</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Plateforme de Génomique, Institut Imagine, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Zarhrate, Mohammed" sort="Zarhrate, Mohammed" uniqKey="Zarhrate M" first="Mohammed" last="Zarhrate">Mohammed Zarhrate</name><affiliation><nlm:affiliation>Plateforme de Génomique, Institut Imagine, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Masson, Cecile" sort="Masson, Cecile" uniqKey="Masson C" first="Cécile" last="Masson">Cécile Masson</name><affiliation><nlm:affiliation>Plateforme de Bioinformatique, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tores, Frederic" sort="Tores, Frederic" uniqKey="Tores F" first="Frédéric" last="Tores">Frédéric Tores</name><affiliation><nlm:affiliation>Plateforme de Bioinformatique, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Blanchet, Patricia" sort="Blanchet, Patricia" uniqKey="Blanchet P" first="Patricia" last="Blanchet">Patricia Blanchet</name><affiliation><nlm:affiliation>Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34090 Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Perez, Marie Jose" sort="Perez, Marie Jose" uniqKey="Perez M" first="Marie-José" last="Perez">Marie-José Perez</name><affiliation><nlm:affiliation>Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34090 Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Petrov, Yuliya" sort="Petrov, Yuliya" uniqKey="Petrov Y" first="Yuliya" last="Petrov">Yuliya Petrov</name><affiliation><nlm:affiliation>Unité de Génétique Médicale et de Cytogénétique, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Nîmes-Hôpital Carémeau, 30029 Nîmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Khau Van Kien, Philippe" sort="Khau Van Kien, Philippe" uniqKey="Khau Van Kien P" first="Philippe" last="Khau Van Kien">Philippe Khau Van Kien</name><affiliation><nlm:affiliation>Unité de Génétique Médicale et de Cytogénétique, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Nîmes-Hôpital Carémeau, 30029 Nîmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Roume, Joelle" sort="Roume, Joelle" uniqKey="Roume J" first="Joelle" last="Roume">Joelle Roume</name><affiliation><nlm:affiliation>Unité de Génétique Médicale, Service de Cytogénétique et de Biologie de la Reproduction, CHI Poissy - St Germain-en-Laye, 78300 Poissy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Leroy, Brigitte" sort="Leroy, Brigitte" uniqKey="Leroy B" first="Brigitte" last="Leroy">Brigitte Leroy</name><affiliation><nlm:affiliation>Service d'Anatomie et de Cytologie Pathologiques, CHI Poissy - St Germain-en-Laye, 78300 Poissy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gribouval, Olivier" sort="Gribouval, Olivier" uniqKey="Gribouval O" first="Olivier" last="Gribouval">Olivier Gribouval</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kalaydjieva, Luba" sort="Kalaydjieva, Luba" uniqKey="Kalaydjieva L" first="Luba" last="Kalaydjieva">Luba Kalaydjieva</name><affiliation><nlm:affiliation>Harry Perkins Institute of Medical Research/Centre for Medical Research, The University of Western Australia, Perth, Nedlands, WA 6009, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Heidet, Laurence" sort="Heidet, Laurence" uniqKey="Heidet L" first="Laurence" last="Heidet">Laurence Heidet</name><affiliation><nlm:affiliation>Assistance Publique - Hôpitaux de Paris, Centre de Référence MARHEA, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Salomon, Remi" sort="Salomon, Remi" uniqKey="Salomon R" first="Rémi" last="Salomon">Rémi Salomon</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; Assistance Publique - Hôpitaux de Paris, Centre de Référence MARHEA, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Antignac, Corinne" sort="Antignac, Corinne" uniqKey="Antignac C" first="Corinne" last="Antignac">Corinne Antignac</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; Assistance Publique - Hôpitaux de Paris, Service de Génétique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Benmerah, Alexandre" sort="Benmerah, Alexandre" uniqKey="Benmerah A" first="Alexandre" last="Benmerah">Alexandre Benmerah</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Saunier, Sophie" sort="Saunier, Sophie" uniqKey="Saunier S" first="Sophie" last="Saunier">Sophie Saunier</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Jeanpierre, Cecile" sort="Jeanpierre, Cecile" uniqKey="Jeanpierre C" first="Cécile" last="Jeanpierre">Cécile Jeanpierre</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France. Electronic address: cecile.jeanpierre@inserm.fr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24439109</idno><idno type="pmid">24439109</idno><idno type="doi">10.1016/j.ajhg.2013.12.017</idno><idno type="wicri:Area/PubMed/Corpus">003937</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003937</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans.</title><author><name sortKey="Humbert, Camille" sort="Humbert, Camille" uniqKey="Humbert C" first="Camille" last="Humbert">Camille Humbert</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Silbermann, Flora" sort="Silbermann, Flora" uniqKey="Silbermann F" first="Flora" last="Silbermann">Flora Silbermann</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Morar, Bharti" sort="Morar, Bharti" uniqKey="Morar B" first="Bharti" last="Morar">Bharti Morar</name><affiliation><nlm:affiliation>Harry Perkins Institute of Medical Research/Centre for Medical Research, The University of Western Australia, Perth, Nedlands, WA 6009, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Parisot, Melanie" sort="Parisot, Melanie" uniqKey="Parisot M" first="Mélanie" last="Parisot">Mélanie Parisot</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Plateforme de Génomique, Institut Imagine, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Zarhrate, Mohammed" sort="Zarhrate, Mohammed" uniqKey="Zarhrate M" first="Mohammed" last="Zarhrate">Mohammed Zarhrate</name><affiliation><nlm:affiliation>Plateforme de Génomique, Institut Imagine, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Masson, Cecile" sort="Masson, Cecile" uniqKey="Masson C" first="Cécile" last="Masson">Cécile Masson</name><affiliation><nlm:affiliation>Plateforme de Bioinformatique, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Tores, Frederic" sort="Tores, Frederic" uniqKey="Tores F" first="Frédéric" last="Tores">Frédéric Tores</name><affiliation><nlm:affiliation>Plateforme de Bioinformatique, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Blanchet, Patricia" sort="Blanchet, Patricia" uniqKey="Blanchet P" first="Patricia" last="Blanchet">Patricia Blanchet</name><affiliation><nlm:affiliation>Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34090 Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Perez, Marie Jose" sort="Perez, Marie Jose" uniqKey="Perez M" first="Marie-José" last="Perez">Marie-José Perez</name><affiliation><nlm:affiliation>Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34090 Montpellier, France.</nlm:affiliation></affiliation></author><author><name sortKey="Petrov, Yuliya" sort="Petrov, Yuliya" uniqKey="Petrov Y" first="Yuliya" last="Petrov">Yuliya Petrov</name><affiliation><nlm:affiliation>Unité de Génétique Médicale et de Cytogénétique, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Nîmes-Hôpital Carémeau, 30029 Nîmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Khau Van Kien, Philippe" sort="Khau Van Kien, Philippe" uniqKey="Khau Van Kien P" first="Philippe" last="Khau Van Kien">Philippe Khau Van Kien</name><affiliation><nlm:affiliation>Unité de Génétique Médicale et de Cytogénétique, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Nîmes-Hôpital Carémeau, 30029 Nîmes, France.</nlm:affiliation></affiliation></author><author><name sortKey="Roume, Joelle" sort="Roume, Joelle" uniqKey="Roume J" first="Joelle" last="Roume">Joelle Roume</name><affiliation><nlm:affiliation>Unité de Génétique Médicale, Service de Cytogénétique et de Biologie de la Reproduction, CHI Poissy - St Germain-en-Laye, 78300 Poissy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Leroy, Brigitte" sort="Leroy, Brigitte" uniqKey="Leroy B" first="Brigitte" last="Leroy">Brigitte Leroy</name><affiliation><nlm:affiliation>Service d'Anatomie et de Cytologie Pathologiques, CHI Poissy - St Germain-en-Laye, 78300 Poissy, France.</nlm:affiliation></affiliation></author><author><name sortKey="Gribouval, Olivier" sort="Gribouval, Olivier" uniqKey="Gribouval O" first="Olivier" last="Gribouval">Olivier Gribouval</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kalaydjieva, Luba" sort="Kalaydjieva, Luba" uniqKey="Kalaydjieva L" first="Luba" last="Kalaydjieva">Luba Kalaydjieva</name><affiliation><nlm:affiliation>Harry Perkins Institute of Medical Research/Centre for Medical Research, The University of Western Australia, Perth, Nedlands, WA 6009, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Heidet, Laurence" sort="Heidet, Laurence" uniqKey="Heidet L" first="Laurence" last="Heidet">Laurence Heidet</name><affiliation><nlm:affiliation>Assistance Publique - Hôpitaux de Paris, Centre de Référence MARHEA, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Salomon, Remi" sort="Salomon, Remi" uniqKey="Salomon R" first="Rémi" last="Salomon">Rémi Salomon</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; Assistance Publique - Hôpitaux de Paris, Centre de Référence MARHEA, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Antignac, Corinne" sort="Antignac, Corinne" uniqKey="Antignac C" first="Corinne" last="Antignac">Corinne Antignac</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; Assistance Publique - Hôpitaux de Paris, Service de Génétique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Benmerah, Alexandre" sort="Benmerah, Alexandre" uniqKey="Benmerah A" first="Alexandre" last="Benmerah">Alexandre Benmerah</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Saunier, Sophie" sort="Saunier, Sophie" uniqKey="Saunier S" first="Sophie" last="Saunier">Sophie Saunier</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Jeanpierre, Cecile" sort="Jeanpierre, Cecile" uniqKey="Jeanpierre C" first="Cécile" last="Jeanpierre">Cécile Jeanpierre</name><affiliation><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France. Electronic address: cecile.jeanpierre@inserm.fr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">American journal of human genetics</title><idno type="eISSN">1537-6605</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Congenital Abnormalities (genetics)</term><term>Congenital Abnormalities (pathology)</term><term>Female</term><term>Fetus (abnormalities)</term><term>Genes, Recessive</term><term>Homozygote</term><term>Humans</term><term>Integrin alpha Chains (genetics)</term><term>Integrin alpha Chains (metabolism)</term><term>Kidney (abnormalities)</term><term>Kidney (pathology)</term><term>Kidney Diseases (congenital)</term><term>Kidney Diseases (genetics)</term><term>Kidney Diseases (pathology)</term><term>Male</term><term>Mutation</term><term>Pedigree</term><term>Urogenital Abnormalities (genetics)</term><term>Urogenital Abnormalities (pathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Integrin alpha Chains</term></keywords><keywords scheme="MESH" qualifier="abnormalities" xml:lang="en"><term>Fetus</term><term>Kidney</term></keywords><keywords scheme="MESH" qualifier="congenital" xml:lang="en"><term>Kidney Diseases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Congenital Abnormalities</term><term>Kidney Diseases</term><term>Urogenital Abnormalities</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Integrin alpha Chains</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Congenital Abnormalities</term><term>Kidney</term><term>Kidney Diseases</term><term>Urogenital Abnormalities</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Female</term><term>Genes, Recessive</term><term>Homozygote</term><term>Humans</term><term>Male</term><term>Mutation</term><term>Pedigree</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24439109</PMID><DateCreated><Year>2014</Year><Month>02</Month><Day>10</Day></DateCreated><DateCompleted><Year>2014</Year><Month>03</Month><Day>31</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1537-6605</ISSN><JournalIssue CitedMedium="Internet"><Volume>94</Volume><Issue>2</Issue><PubDate><Year>2014</Year><Month>Feb</Month><Day>06</Day></PubDate></JournalIssue><Title>American journal of human genetics</Title><ISOAbbreviation>Am. J. Hum. Genet.</ISOAbbreviation></Journal><ArticleTitle>Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans.</ArticleTitle><Pagination><MedlinePgn>288-94</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ajhg.2013.12.017</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0002-9297(13)00614-9</ELocationID><Abstract><AbstractText>Renal hypodysplasia (RHD) is a heterogeneous condition encompassing a spectrum of kidney development defects including renal agenesis, hypoplasia, and (cystic) dysplasia. Heterozygous mutations of several genes have been identified as genetic causes of RHD with various severity. However, these genes and mutations are not associated with bilateral renal agenesis, except for RET mutations, which could be involved in a few cases. The pathophysiological mechanisms leading to total absence of kidney development thus remain largely elusive. By using a whole-exome sequencing approach in families with several fetuses with bilateral renal agenesis, we identified recessive mutations in the integrin α8-encoding gene ITGA8 in two families. Itga8 homozygous knockout in mice is known to result in absence of kidney development. We provide evidence of a damaging effect of the human ITGA8 mutations. These results demonstrate that mutations of ITGA8 are a genetic cause of bilateral renal agenesis and that, at least in some cases, bilateral renal agenesis is an autosomal-recessive disease.</AbstractText><CopyrightInformation>Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Humbert</LastName><ForeName>Camille</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Silbermann</LastName><ForeName>Flora</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morar</LastName><ForeName>Bharti</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Harry Perkins Institute of Medical Research/Centre for Medical Research, The University of Western Australia, Perth, Nedlands, WA 6009, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Parisot</LastName><ForeName>Mélanie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Plateforme de Génomique, Institut Imagine, Hôpital Necker-Enfants Malades, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zarhrate</LastName><ForeName>Mohammed</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Plateforme de Génomique, Institut Imagine, Hôpital Necker-Enfants Malades, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Masson</LastName><ForeName>Cécile</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Plateforme de Bioinformatique, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tores</LastName><ForeName>Frédéric</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Plateforme de Bioinformatique, Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blanchet</LastName><ForeName>Patricia</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34090 Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perez</LastName><ForeName>Marie-José</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Département de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34090 Montpellier, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petrov</LastName><ForeName>Yuliya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Unité de Génétique Médicale et de Cytogénétique, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Nîmes-Hôpital Carémeau, 30029 Nîmes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khau Van Kien</LastName><ForeName>Philippe</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Unité de Génétique Médicale et de Cytogénétique, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU de Nîmes-Hôpital Carémeau, 30029 Nîmes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roume</LastName><ForeName>Joelle</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Unité de Génétique Médicale, Service de Cytogénétique et de Biologie de la Reproduction, CHI Poissy - St Germain-en-Laye, 78300 Poissy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leroy</LastName><ForeName>Brigitte</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Service d'Anatomie et de Cytologie Pathologiques, CHI Poissy - St Germain-en-Laye, 78300 Poissy, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gribouval</LastName><ForeName>Olivier</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kalaydjieva</LastName><ForeName>Luba</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Harry Perkins Institute of Medical Research/Centre for Medical Research, The University of Western Australia, Perth, Nedlands, WA 6009, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heidet</LastName><ForeName>Laurence</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Assistance Publique - Hôpitaux de Paris, Centre de Référence MARHEA, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salomon</LastName><ForeName>Rémi</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; Assistance Publique - Hôpitaux de Paris, Centre de Référence MARHEA, Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Antignac</LastName><ForeName>Corinne</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France; Assistance Publique - Hôpitaux de Paris, Service de Génétique, Hôpital Necker-Enfants Malades, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benmerah</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saunier</LastName><ForeName>Sophie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeanpierre</LastName><ForeName>Cécile</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale U983, Hôpital Necker-Enfants Malades, 75015 Paris, France; Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, 75015 Paris, France. Electronic address: cecile.jeanpierre@inserm.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>01</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Am J Hum Genet</MedlineTA><NlmUniqueID>0370475</NlmUniqueID><ISSNLinking>0002-9297</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C579157">ITGA8 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D039001">Integrin alpha Chains</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C093856">integrin alpha8</NameOfSubstance></Chemical></ChemicalList><SupplMeshList><SupplMeshName Type="Disease" UI="C536482">Hereditary renal agenesis</SupplMeshName><SupplMeshName Type="Disease" UI="C563261">Renal Adysplasia</SupplMeshName></SupplMeshList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>Am J Hum Genet. 2014 May 1;94(5):799</RefSource></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mutat. 2011 Feb;32(2):183-90</RefSource><PMID Version="1">21280147</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2009 May 22;284(21):14524-36</RefSource><PMID Version="1">19342381</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS One. 2009;4(10):e7313</RefSource><PMID Version="1">19809516</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Int J Nephrol. 2012;2012:909083</RefSource><PMID 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MajorTopicYN="N">Integrin alpha Chains</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007668" MajorTopicYN="N">Kidney</DescriptorName><QualifierName UI="Q000002" MajorTopicYN="Y">abnormalities</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007674" MajorTopicYN="N">Kidney Diseases</DescriptorName><QualifierName UI="Q000151" MajorTopicYN="Y">congenital</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010375" 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