Yao Ke, Jin Chongfei, Zhu Ning, Wang Wei, Wu Renyi, Jiang Jin, Shentu Xingchao
Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
Mol Vis. 2008 Jul 9;14:1272-6.
To identify the genetic defect associated with autosomal dominant congenital nuclear cataract in a Chinese family.
Family history and phenotypic data were recorded, and the phenotypes were documented by slit lamp photography. The genomic DNA was extracted from peripheral blood leukocytes. All the exons and flanking intronic sequences of CRYGC and CRYGD were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Structural models of the wild type and mutant gammaC-crystallin were generated and analyzed by SWISS-MODEL.
Sequencing of the coding regions of CRYGC and CRYGD showed the presence of a heterozygous C>A transversion at c.327 of the coding sequence in exon 3 of CRYGC (c.327C>A), which results in the substitution of a wild type cysteine to a nonsense codon (C109X). One and a half Greek key motifs at the COOH-terminus were found to be absent in the structural model of the mutant truncated gammaC-crystallin.
A novel nonsense mutation in CRYGC was detected in a Chinese family with consistent autosomal dominant congenital nuclear cataract, providing clear evidence of a relationship between the genotype and the corresponding cataract phenotype.
确定一个中国家系中与常染色体显性遗传性先天性核性白内障相关的基因缺陷。
记录家族史和表型数据，通过裂隙灯照相记录表型。从外周血白细胞中提取基因组DNA。通过聚合酶链反应（PCR）扩增CRYGC和CRYGD的所有外显子及侧翼内含子序列，并通过直接DNA测序筛选突变。利用SWISS-MODEL生成并分析野生型和突变型γC-晶状体蛋白的结构模型。
CRYGC和CRYGD编码区测序显示，CRYGC第3外显子编码序列的c.327处存在杂合的C>A颠换（c.327C>A），导致野生型半胱氨酸被无义密码子取代（C109X）。在突变型截短γC-晶状体蛋白的结构模型中，发现COOH末端缺少一个半希腊钥匙基序。
在一个患有常染色体显性遗传性先天性核性白内障的中国家系中检测到CRYGC基因的一个新的无义突变，为基因型与相应白内障表型之间的关系提供了明确证据。
