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A study of PITX3 gene mutation in five families has improved our understanding of heritable cataracts. Genetic researchers have identified a unique, recurrent mutation at chromosome 10q25 to account for posterior polar cataract (CPP4) that occurs across ethnic groups. The study also indicates a bigger role for PITX3 in the development of the lens of the eye than the rest of the anterior segment, as all subjects with the mutation had cataracts.
This PITX3 mutation occurred in four unrelated large families with autosomal dominant posterior polar cataract, three English and one Chinese, and segregated with family members affected by cataracts. Two of the families had members with anterior/segment mesenchymal dysgenesis (ASMD). The mutation is a 17 base pair duplication in exon 4 of the PITX3 gene that results in a frameshift at codon 220 and altered protein product with 94 extra amino acid residues. The fifth family, of Hispanic origin, had a novel mutation in exon 4—650delG—which segregated with cataract. Neither mutation occurred in 100 healthy controls.
All family members had a full clinical examination and were genotyped. Amplification of DNA of the PITX3 region was followed by direct sequencing of the amplification products.
Cataract is the commonest form of blindness. More than 14 distinct loci have been identified in humans for 11 different types of autosomal dominant congenital cataracts. Mutation in the gene for developmental transcription factor PITX3 is one more in an array of mutations in eye proteins causing the condition.
Berry V, et al. Journal of Medical Genetics 2004;41:e109 (http://www.jmedgenet.com/cgi/content/full/41/8/e109)