title: A novel mutation in GJA1 causing oculodentodigital syndrome and primary lymphoedema in a three generation family.
abstract: Oculodentodigital syndrome (ODD; OMIM 164200) is a congenital condition with phenotypic features most commonly affecting the face, eyes, dentition and digits. The condition is caused by mutations in the GJA1 gene on chromosome 6. GJA1 codes for connexin 43, a gap junction protein important in providing cell to cell communication and is expressed in lymphatic valves. We present a patient with a clinical and molecular diagnosis of ODD and lower limb lymphoedema. Sanger sequencing of family members confirmed that the missense, p.K206R, GJA1 mutation segregated with the phenotype suggestive of causality. To our knowledge this association has not been reported previously. This is therefore the second connexin gene associated with a lymphoedema phenotype after the recent publication of GJC2 (connexin 47) as a cause of four limb lymphoedema.
authors.affiliation: SW Thames Regional Genetics Service.
authors.forename: G
authors.initials: G
authors.lastname: Brice
authors.forename: P
authors.initials: P
authors.lastname: Ostergaard
authors.forename: S
authors.initials: S
authors.lastname: Jeffery
authors.forename: K
authors.initials: K
authors.lastname: Gordon
authors.forename: P S
authors.initials: PS
authors.lastname: Mortimer
authors.forename: S
authors.initials: S
authors.lastname: Mansour
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D018031:Connexin 43 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005091:Exons; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005532:Foot Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008209:Lymphedema / Q000175:diagnosis / Q000235:genetics*; D061305:Lymphoscintigraphy; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013576:Syndactyly / Q000175:diagnosis / Q000235:genetics*; D014071:Tooth Abnormalities / Q000175:diagnosis / Q000235:genetics*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human
keywords: GJA1; ODD syndrome; connexin 43; lymphoedema; oculodentodigital syndrome