1. Matthew-Wood Syndrome Is Caused by Truncating Mutations in the Retinol-Binding Protein Receptor Gene STRA6
- Author
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Michel Vekemans, Christelle Golzio, Bettina Grattagliano-Bessières, Jelena Martinovic-Bouriel, Arnold Munnich, Sophie Delahaye, Tania Attié-Bitach, Stanislas Lyonnet, Heather C. Etchevers, Soumaya Mougou-Zrelli, Maryse Bonnière, Férechté Encha-Razavi, Sophie Thomas, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Institut de Puériculture de Paris (IPP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Puériculture de Paris ( IPP ), and Assistance publique - Hôpitaux de Paris (AP-HP)
- Subjects
Lung Diseases ,MESH: Sequence Analysis, DNA ,Vitamin A transport ,MESH : Polymorphism, Genetic ,MESH : Receptors, Cell Surface ,MESH : Gene Deletion ,MESH: Genetic Markers ,MESH : Syndrome ,MESH : Frameshift Mutation ,MESH : Microphthalmos ,Consanguinity ,MESH: Lung Diseases ,Exon ,MESH : Exons ,0302 clinical medicine ,Microphthalmos ,MESH : Genetic Markers ,MESH: Syndrome ,Genetics(clinical) ,Frameshift Mutation ,Genetics (clinical) ,MESH: Receptors, Cell Surface ,0303 health sciences ,Fetal Growth Retardation ,MESH : Lung Diseases ,Homozygote ,MESH: Frameshift Mutation ,Exons ,Syndrome ,Pedigree ,MESH: Membrane Proteins ,MESH : Mutation ,MESH: Homozygote ,Genetic Markers ,MESH: Abnormalities, Multiple ,MESH: Mutation ,MESH: Pedigree ,MESH: Microphthalmos ,MESH: Fetal Growth Retardation ,Receptors, Cell Surface ,Biology ,Frameshift mutation ,03 medical and health sciences ,Pulmonary hypoplasia ,MESH : Homozygote ,Report ,MESH : Consanguinity ,MESH: Polymorphism, Genetic ,Genetics ,medicine ,Humans ,Abnormalities, Multiple ,MESH : Fetal Growth Retardation ,MESH : Haplotypes ,030304 developmental biology ,MESH: Consanguinity ,MESH : Mutagenesis, Insertional ,Polymorphism, Genetic ,MESH: Humans ,Anophthalmia ,MESH : Abnormalities, Multiple ,Genetic heterogeneity ,MESH : Humans ,Pulmonary Agenesis ,Membrane Proteins ,Sequence Analysis, DNA ,MESH: Haplotypes ,medicine.disease ,Molecular biology ,Mutagenesis, Insertional ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Haplotypes ,MESH: Mutagenesis, Insertional ,MESH : Membrane Proteins ,MESH: Gene Deletion ,MESH : Pedigree ,[ SDV.BDD.EO ] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Mutation ,MESH: Exons ,Matthew Wood syndrome ,Gene Deletion ,030217 neurology & neurosurgery ,MESH : Sequence Analysis, DNA - Abstract
International audience; Retinoic acid (RA) is a potent teratogen in all vertebrates when tight homeostatic controls on its endogenous dose, location, or timing are perturbed during early embryogenesis. STRA6 encodes an integral cell-membrane protein that favors RA uptake from soluble retinol-binding protein; its transcription is directly regulated by RA levels. Molecular analysis of STRA6 was undertaken in two human fetuses from consanguineous families we previously described with Matthew-Wood syndrome in a context of severe microphthalmia, pulmonary agenesis, bilateral diaphragmatic eventration, duodenal stenosis, pancreatic malformations, and intrauterine growth retardation. The fetuses had either a homozygous insertion/deletion in exon 2 or a homozygous insertion in exon 7 predicting a premature stop codon in STRA6 transcripts. Five other fetuses presenting at least one of the two major signs of clinical anophthalmia or pulmonary hypoplasia with at least one of the two associated signs of diaphragmatic closure defect or cardiopathy had no STRA6 mutations. These findings suggest a molecular basis for the prenatal manifestations of Matthew-Wood syndrome and suggest that phenotypic overlap with other associations may be due to genetic heterogeneity of elements common to the RA- and fibroblast growth factor-signaling cascades.
- Published
- 2007