Genotype-phenotype correlations for cataracts in neurofibromatosis 2.

N eurofibromatosis 2 (NF2) is an autosomal dominant disease that is caused by inactivating mutations of the NF2 tumour suppressor gene. 2 Multiple central and peripheral nervous system tumours and ocular abnormalities are common in NF2; bilateral vestibular schwannomas are pathognomonic for the disease. Genotype-phenotype correlations are well established for NF2 associated tumours. In general, constitutional nonsense or frameshift NF2 mutations are associated with severe NF2 (that is, earlier onset of symptoms and more tumours), splice site mutations with variable disease severity, and missense mutations with mild disease. Genotype-phenotype correlations have not been reported for the non-tumour manifestations of NF2. The most common of these manifestations is presenile cataracts, which occur in about 60–80% of people with NF2. In animal models, lens fibre cells that are more differentiated express less Nf2 protein than the epithelial regions of the lens, suggesting that the Nf2 protein may play a role in lens epithelial cell migration or elongation. The purpose of this study was to determine if there were genotype-phenotype correlations for cataracts in NF2.