Shandong Eye Institute, Qingdao University Eye College, China.
Hum Mutat. 2011 Jan;32(1):E1939-47. doi: 10.1002/humu.21386.
To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family, molecular genetic investigation via haplotype analysis and direct sequencing were performed Sequencing of the CRYGD gene revealed a c.127T>C transition, which resulted in a substitution of a highly conserved tryptophan with arginine at codon 43 (p.Trp43Arg). This mutation co-segregated with all affected individuals and was not observed in either unaffected family members or in 200 normal unrelated individuals. Biophysical studies indicated that the p.Trp43Arg mutation resulted in significant tertiary structural changes. The mutant protein was much less stable than the wild-type protein, and was more prone to aggregate when subjected to environmental stresses such as heat and UV irradiation.
为了鉴定一个中国家族中常染色体显性先天性核性白内障相关的基因缺陷，通过单倍型分析和直接测序进行了分子遗传学研究。CRYGD 基因的测序显示 c.127T>C 转换，导致高度保守的色氨酸被精氨酸取代，在密码子 43（p.Trp43Arg）。该突变与所有受影响个体共分离，在未受影响的家庭成员或 200 名正常无关个体中均未观察到。生物物理研究表明，p.Trp43Arg 突变导致显著的三级结构变化。突变蛋白的稳定性明显低于野生型蛋白，在受到热和紫外线照射等环境应激时更容易聚集。
