A Splice Site Mutation in CRYBA1/A3 Causing Autosomal Dominant Posterior Polar Cataract in a Chinese Pedigree

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2010 Feb 10

PMID 20142846

Citations 18

Authors

Zhensheng Gu

Baohu Ji

Chunling Wan

Guang He

Juan Zhang

Ming Zhang

Guoyin Feng

Lin He

Linghan Gao

Affiliations

Soon will be listed here.

Abstract

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 (Z(max)) 2.02 at D17S1800 (theta(max)=0.00). Haplotyping identified a 26-cM region flanked by D17S921 and D17S800 on 17p12-21.2, namely at the betaA1/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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