Xu Wei-zhen, Zheng Shu, Xu Shi-jie, Huang Wei, Yao Ke, Zhang Su-zhan
Cancer Institute, Zhejiang University College of Medicine, Zhejiang University, Hangzhou, PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004 Feb;21(1):19-22.
To identify the genetic defect for the autosomal dominant coralliform cataract affecting a four-generation Chinese family.
Genomic DNA from the family members was typed for whole genomic linkage analysis. Two-point LOD scores were calculated using the LINKAGE program package (version 5.1). Mutation analysis of candidate genes was performed by direct sequencing.
Thirteen of the 38 individuals had congenital cataracts. The maximum two point LOD score, 3.5 at theta=0.1 was obtained for the marker D2S325. Mutation analysis of the gamma-crystallin gene cluster identified a C --> A mutation in exon 2 of gamma-D crystallin gene (CRYGD) associated with cataracts in this family. This mutation resulted in a substitution of threonine for proline at amino acid 23 (P23T) of the protein.
The results suggest that the coralliform cataract phenotype is due to a mutated gamma-D gene, and the sequence change is identical with that recently reported to be related with lamellar cataract, a distinct clinical entity, thus providing evidence that the same genetic defect may be associated with different opacity location. The pathogenesis needs further investigation.
确定一个四代中国人家族中常染色体显性遗传珊瑚状白内障的基因缺陷。
对家族成员的基因组DNA进行全基因组连锁分析分型。使用LINKAGE程序包（版本5.1）计算两点LOD分数。通过直接测序对候选基因进行突变分析。
38名个体中有13人患有先天性白内障。标记D2S325在θ=0.1时获得的最大两点LOD分数为3.5。γ-晶体蛋白基因簇的突变分析在γ-D晶体蛋白基因（CRYGD）的外显子2中鉴定出一个与该家族白内障相关的C→A突变。该突变导致蛋白质第23位氨基酸（P23T）处的脯氨酸被苏氨酸取代。
结果表明，珊瑚状白内障表型是由于γ-D基因突变所致，且该序列变化与最近报道的与板层状白内障（一种不同的临床实体）相关的变化相同，从而提供了证据表明相同的基因缺陷可能与不同的混浊部位相关。其发病机制需要进一步研究。
