title: Matthew-Wood syndrome is caused by truncating mutations in the retinol-binding protein receptor gene STRA6.
abstract: 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.
authors.affiliation: INSERM U781, Hopital Necker, Paris Cedex, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Golzio
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic-Bouriel
authors.forename: Sophie
authors.initials: S
authors.lastname: Thomas
authors.forename: Soumaya
authors.initials: S
authors.lastname: Mougou-Zrelli
authors.forename: Bettina
authors.initials: B
authors.lastname: Grattagliano-Bessieres
authors.forename: Maryse
authors.initials: M
authors.lastname: Bonniere
authors.forename: Sophie
authors.initials: S
authors.lastname: Delahaye
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Ferechte
authors.initials: F
authors.lastname: Encha-Razavi
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Vekemans
authors.forename: Tania
authors.initials: T
authors.lastname: Attie-Bitach
authors.forename: Heather C
authors.initials: HC
authors.lastname: Etchevers
mesh_terms: D000015:Abnormalities, Multiple; D003241:Consanguinity; D005091:Exons; D005317:Fetal Growth Retardation / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D005819:Genetic Markers; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008171:Lung Diseases / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008850:Microphthalmos / Q000235:genetics* / Q000473:pathology; D016254:Mutagenesis, Insertional; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013577:Syndrome
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C519685:STRA6 protein, human; C027928:retinol binding protein receptor