A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome

BACKGROUND: Oculodentodigital syndrome (ODD) is a pleiotropic congenital disorder characterised by abnormalities of the face, eyes, dentition, and limbs. ODD, which is inherited as an autosomal dominant trait, results from missense mutations in the gap junction protein connexin 43.

OBJECTIVE: To analyse a family with a history of ODD which is inherited in an autosomal recessive manner

RESULTS: ODD in this family resulted from the homozygous mutation R33X in the first transmembrane domain of connexin 43.

CONCLUSIONS: The findings provide clear genetic evidence that ODD can be inherited in an autosomal recessive manner and that a dominant negative mechanism underlies autosomal dominant ODD.