Cerulean cataract mapped to 12q13 and associated with a novel initiation codon mutation in MIP

PURPOSE To identify the genetic defect in a large Chinese family with autosomal dominant cerulean cataract. METHODS Genomic DNA and clinical data were collected from the family. Candidate gene sequencing and genome-wide linkage analysis were used to disclose the molecular basis responsible for cerulean cataract in the family. RESULTS Initially, sequencing analysis of the three genes (beta-B2-crystallin [CRYBB2], gamma-D-crystallin [CRYGD], and V-MAF avian musculoaponeurotic fibrosarcoma oncogene homolog [MAF]) known to cause cerulean cataract failed to find any mutation. Then, genome-wide linkage analysis mapped the disease to chromosome 12q13-q22 between D12S85 and D12S351, with a maximum lod score of 4.10 at θ=0. Sequence analysis of the major intrinsic protein of lens fiber gene (MIP), a gene known to cause other types of cataract in the linkage interval, detected a novel heterozygous initiation codon mutation, c.2T>C (p.Met1?). This mutation was present in all patients with cerulean cataract but was not present in any of the 13 unaffected family members nor in 96 control individuals. CONCLUSIONS Cerulean cataract was found in a large family and is caused by a novel initiation codon mutation in MIP. This study adds a new member in the existing list of genes causing cerulean cataract and expands the mutation spectrum and phenotypic association of MIP mutations.