Yang Guoxing, Xiong Chunlei, Li Shanlan, Wang Yuanyuan, Zhao Jialiang
Department of Opthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Mol Vis. 2011 Apr 28;17:1085-9.
Congenital cataract is a clinically and genetically heterogeneous lens disorder. The purpose of this study was to identify the mutation responsible for autosomal dominant congenital coralliform cataracts in two Chinese families and to investigate the relationship between virulence genes and lens morphology.
Patients received a physical examination, and blood samples were collected for DNA extraction. Mutation analysis was performed by direct sequencing of the candidate genes: gammaC-crystallin (CRYGC), gammaD-crystallin (CRYGD), gammaS-crystallin (CRYGS), gap-junction protein, alpha 8 (GJA8), gap-junction protein, alpha 3 (GJA3), and alphaA-crystallin (CRYAA).
The affected individuals in two families had congenital coralliform cataracts. Mutational analysis of the CRYGD identified a C→A transversion at nucleotide position c.70 in exon 2, which resulted in a threonine substitution for proline at amino-acid residue 24 (P24T). This mutation was identified in all affected individuals but was not found in healthy relatives or 100 control chromosomes from the same ethnic background.
Our results indicated that the P24T mutation of CRYGD was responsible for two Chinese pedigrees with congenital coralliform cataracts. CRYGD and coralliform cataracts are highly related, and P24T may be a hot-point mutation for this disorder.
先天性白内障是一种临床和遗传异质性晶状体疾病。本研究旨在确定两个中国家系中常染色体显性遗传性先天性珊瑚状白内障的致病突变，并探讨致病基因与晶状体形态之间的关系。
对患者进行体格检查，并采集血样用于DNA提取。通过对候选基因进行直接测序来进行突变分析，这些候选基因包括：γC-晶状体蛋白（CRYGC）、γD-晶状体蛋白（CRYGD）、γS-晶状体蛋白（CRYGS）、缝隙连接蛋白α8（GJA8）、缝隙连接蛋白α3（GJA3）和αA-晶状体蛋白（CRYAA）。
两个家系中的患病个体均患有先天性珊瑚状白内障。对CRYGD进行突变分析时，在外显子2的核苷酸位置c.70处发现了一个C→A的颠换，导致氨基酸残基24处的脯氨酸被苏氨酸取代（P24T）。在所有患病个体中均发现了该突变，但在健康亲属或来自相同种族背景的100条对照染色体中未发现。
我们的结果表明，CRYGD基因的P24T突变是两个中国家系先天性珊瑚状白内障的致病原因。CRYGD与珊瑚状白内障高度相关，P24T可能是该疾病的一个热点突变。
