Purpose: To identify the underlying genetic defect in a three-generation family with five members affected with dominant bilateral congenital cataract and microcornea.
Methods: Detailed family history and clinical data were recorded. Mutation screening in the candidate genes, CRYAA, CRYBB1, MAF, GJA3, and GJA8, was performed by bidirectional sequencing of the amplified products.
Results: Affected individuals had a jellyfish-like cataract in association with microcornea. Sequencing of GJA8 (connexin 50) showed a novel, heterozygous c.134G-->C change that resulted in the substitution of a highly conserved tryptophan by serine (p.W45S). This sequence change segregated completely with the disease phenotype and was not observed in 108 ethnically matched controls (216 chromosomes). However, an identical substitution has previously been described in GJA3 (connexin 46) leading to autosomal dominant nuclear cataract without microcornea.
Conclusions: This is a novel mutation identified in the first transmembrane domain (M1) of GJA8. These findings further expand the mutation spectrum of connexin 50 (Cx50) in association with congenital cataract and microcornea.