A novel P20R mutation in the alpha-B crystallin gene causes autosomal dominant congenital posterior polar cataracts in a Chinese family

作者：Xia, Xin-Yi; Wu, Qiu-Yue; An, Li-Mei; Li, Wei-Wei; Li, Na; Li, Tian-Fu; Zhang, Cui; Cui, Ying-Xia; Li, Xiao-Jun^*; Xue, Chun-Yan

来源：BMC Ophthalmology, 2014, 14(1): 108.

DOI：10.1186/1471-2415-14-108

• Congenital posterior polar cataract
• Alpha-B crystallin gene
• P20R mutation

Background: To identify the genetic defects and investigate the possible mechanism of cataract genesis in a five-generation family with autosomal dominant congenital posterior polar cataracts. @@@ Methods: Clinical data were collected, and the lens phenotypes of the affected members in this family were recorded by slit lamp photography. Genomic DNA was isolated from peripheral blood using QIAamp DNA Blood Mini Kits. Twenty-three mutational hot spots associated with autosomal dominant congenital posterior polar cataracts were screened by PCR-based DNA sequencing. Properties and structural models of wild-type and mutant alpha-B (alpha B)-crystallin (CRYAB) were generated and analyzed using SWISS-MODEL. @@@ Results: All affected individuals in this family started to exhibit poor vision at the age of 8-10 years. The lens opacity consisted of a single, well-defined plaque, 0.5-3 mm in diameter, which was confined to the posterior pole of the lens. DNA sequencing analysis of the affected members showed a novel, heterozygous missense mutation c.59C > G (P20R) in exon 1 of the CRYAB gene. This mutation was not found in 10 unaffected family members, or in 200 unaffected and unrelated individuals, thereby excluding the possibility that it is a rare polymorphism. Data generated using the ProtScale and PyMOL programs revealed that the mutation altered the stability and solubility of the alpha B-crystallin protein. @@@ Conclusions: This study reported a novel c.59C > G (P20R) missense mutation in CRYAB in a five-generation Chinese family with posterior polar cataract.

• 出版日期2014-9-8
• 单位南京大学