title: Oculo-dento-digital dysplasia: lack of genotype-phenotype correlation for GJA1 mutations and usefulness of neuro-imaging.
abstract: Oculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder with complete penetrance and high intra- and interfamilial phenotypic variability. The key features in this syndrome are microphthalmia, enamel hypoplasia and syndactyly of the 4th-5th fingers. ODDD is caused by mutations in the connexin 43 gene (GJA1). We report here four patients from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patients had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leads us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement.
authors.affiliation: Université Victor Segalen Bordeaux 2, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Alao
authors.forename: D
authors.initials: D
authors.lastname: Bonneau
authors.forename: M
authors.initials: M
authors.lastname: Holder-Espinasse
authors.forename: C
authors.initials: C
authors.lastname: Goizet
authors.forename: S
authors.initials: S
authors.lastname: Manouvrier-Hanu
authors.forename: A
authors.initials: A
authors.lastname: Mezel
authors.forename: F
authors.initials: F
authors.lastname: Petit
authors.forename: D
authors.initials: D
authors.lastname: Subtil
authors.forename: C
authors.initials: C
authors.lastname: Magdelaine
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002675:Child, Preschool; D018031:Connexin 43 / Q000235:genetics*; D003744:Dental Enamel Hypoplasia / Q000235:genetics; D003952:Diagnostic Imaging; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005385:Fingers / Q000002:abnormalities; D005838:Genotype; D006801:Humans; D007021:Hypospadias / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013576:Syndactyly / Q000235:genetics*; D014071:Tooth Abnormalities / Q000235:genetics*; D055815:Young Adult
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human