Purpose: To identify the mutant gene for autosomal dominant posterior polar congenital cataract in a four-generation Chinese pedigree. Methods: The clinical data of patients from the family were recorded by slit-lamp photography. Genomic DNA samples from peripheral blood of the pedigree members were then isolated to map the relevant gene, using microsatellite markers for two-point linkage analysis. Genotype and haplotypes of the pedigree were constructed using Cyrillic software to locate the relevant region. Direct sequencing was performed to screen out the disease-causing mutation. Results: The congenital cataract phenotype of the pedigree was labeled as the posterior polar type by using slit-lamp photography. Linkage analysis results indicated a maximum logarithm of odds LOD score of (Zmax) 2.02 at D17S1800 (θmax=0.00). Haplotyping identified a 26-cM region flanked by D17S921 and D17S800 on 17p12-21.2, namely at the βA1/A3-crystallin (CRYBA1/A3) gene locus. Sequencing revealed a splice site mutation, G→A, at the first base of intron 3 of CRYBA1/A3, which co-segregated with the affected individuals in the pedigree but which was not found in the unaffected members of the family or in the 50 unrelated controls. Conclusions: Our results demonstrated that a splice site mutation of CRYBA1/A3 was responsible for the autosomal dominant posterior polar congenital cataract in a four-generation Chinese pedigree. The same mutation in this gene had previously been reported to be associated with other phenotype cataracts. This study is the first report relating a mutation of CRYBA1/A3 to posterior polar cataract.
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