Guo Yuanyuan, Su Dongmei, Li Qian, Yang Zhenfei, Ma Zicheng, Ma Xu, Zhu Siquan
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.
Mol Vis. 2012;18:1874-80. Epub 2012 Jul 11.
To report the identification of a nonsense mutation in γC-crystallin (CRYGC) associated with autosomal dominant congenital nuclear cataracts and microcornea in a Chinese family.
We investigated four generations of a Chinese family six of whose members were affected by nuclear cataracts and microcornea. The genomic DNA was extracted from peripheral blood leukocytes. All reported nuclear cataract-related candidate genes were screened for causative mutations by direct DNA sequencing. The effects of amino acid changes on the structure and function of proteins were predicted by bioinformatics analysis.
All affected individuals in this family exhibited nuclear cataracts and microcornea. Direct sequencing of the candidate gene cluster showed a c.471G>A transition in exon 3 of CRYGC, which co-segregated according to family members with cataracts, and was not observed in 100 normal controls. This single nucleotide change was predicted to introduce a translation stop codon at tryptophan 157 (W157X). Bioinformatics analysis showed that the mutation was predicted to affect the function and secondary structure of the CRYGC protein.
This study identified a disease-causing mutation c.471G>A in CRYGC in a Chinese family with cataracts, expanding the mutation spectrum of CRYGC causing congenital cataracts.
报告在中国一个家族中鉴定出与常染色体显性先天性核性白内障和小角膜相关的γC-晶状体蛋白（CRYGC）无义突变。
我们调查了一个中国家族的四代人，其中六名成员患有核性白内障和小角膜。从外周血白细胞中提取基因组DNA。通过直接DNA测序筛选所有已报道的与核性白内障相关的候选基因，以寻找致病突变。通过生物信息学分析预测氨基酸变化对蛋白质结构和功能的影响。
该家族中所有受影响个体均表现出核性白内障和小角膜。对候选基因簇进行直接测序显示，CRYGC第3外显子存在c.471G>A转换，该突变与患白内障的家庭成员共分离，且在100名正常对照中未观察到。这一单核苷酸变化预计会在色氨酸157（W157X）处引入翻译终止密码子。生物信息学分析表明，该突变预计会影响CRYGC蛋白的功能和二级结构。
本研究在中国一个白内障家族中鉴定出CRYGC基因致病突变c.471G>A，扩大了导致先天性白内障的CRYGC基因突变谱。
