Novel MAF mutation in a family with congenital cataract-microcornea syndrome.

PURPOSE: To further unravel the molecular genetic background for the association congenital cataract-microcornea (CCMC).
METHODS: DNA variation was pointed out by direct DNA sequencing of 13 lens-expressed cataract genes from three CCMC families and one isolated case. The mutation screening included seven crystalline genes, two gap junction protein genes, and four lens expressed regulatory genes.
RESULTS: A DNA variation in the basic leucine zipper transcription factor V-maf musculoaponeurotic fibrosarcoma oncogene homolog gene (MAF) was identified in one family. The mutation c.895C>A changes arginine 299 to a serine residue, and the substitution destroys the basic region of the DNA binding domain of MAF leucine-zipper. Mutations were not identified in the remaining CCMC patients.
CONCLUSIONS: One novel mutation affecting a known cataract gene was identified among four unrelated individuals with presumed autosomal dominant congenital cataract-microcornea syndrome. The MAF mutation p.Arg299Ser is the third mutation identified in association with the CCMC phenotype, and all three mutations are located in the basic region of the DNA binding domain in the MAF protein (OMIM 177075). This suggests that the basic region is a hot spot domain for CCMC associated mutations. The identification of a novel mutation associated with the distinct cataract-microcornea phenotype adds a new brick to the puzzle of molecular modeling of the lens-anterior segment structures.