A novel GJA1 mutation causes oculodentodigital dysplasia without syndactyly

Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant pleiotropic disorder, caused by mutations in the Connexin 43 gene (GJA1) [Paznekas et al. (2003): Am J Hum Genet 72:408-418], which is localized to human chromosome 6q22-q23. Here, we describe the identification of a novel heterozygous missense mutation in the GJA1 gene, (H194P) in an Italian family previously reported to be affected by isolated autosomal dominant microphthalmia [Vingolo et al. (1994): J Med Genet 31:721-725]. Careful clinical re-evaluation revealed that this family shows an atypical form of ODDD, characterized by the predominance of the ocular involvement and by the absence of hand and/or foot syndactyly. The mutation affects an amino acid residue localized in the second extracellular domain of the Cx43 protein and highly conserved across evolution. This finding confirms the highly variable phenotypic expression caused by GJA1 mutations.