A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features

Oculodentodigital dysplasia (ODDD) is an autosomal dominant disorder that includes a clinical spectrum of craniofacial, neurologic, limb, and ocular malformations. The disease is caused by heterozygous mutations in the 6q22-q23 located GJA1 gene, that encodes connexin 43 (Cx43). In this paper we describe a novel Cx43 mutation (G2V) found in a Mexican eight-year-old boy. This de novo mutation predicts a missense substitution at the second amino acid of Cx43, in the first intracellular domain, and is the most amino-terminal located mutation reported so far. Umbilical hernia and congenital optociliary veins, two uncommon ODDD-associated features, were recognized in our patient. The phenotype of three previously described patients with Cx43 first intracellular domain mutation is discussed and compared with that observed in our patient. This case expands the phenotypic and genotypic spectrum of ODDD.