Lin Ying, Liu Ni-ni, Lei Chun-tao, Fan Ying-chuan, Liu Xiao-qi, Yang Yang, Wang Jun-fang, Liu Bing, Yang Zheng-lin
Sichuan Academy of Medical Science & Sichuan Provincial Peoples' Hospital, Chengdu, Sichuan, 610072 People's Republic of China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Feb;25(1):59-62.
To identify the mutations in the gap junction protein alpha3/alpha8 gene (GJA3 or GJA8) in the Chinese family with autosomal dominant congenital cataract (ADCC).
All subjects(5 family members and 100 unrelated control individuals)were undergone comprehensive ophthalmic examination, and genomic DNA was extracted from peripheral blood (5 mL). The exons and flanking introns of GJA3/GJA8 genes were amplified by polymerase chain reaction (PCR). Purified PCR products were then sequenced directly for screening disease-causing mutations.
Upon bidirectional sequence analysis, a G-->A transition at nucleotide 138 (c.138G>A)in exon 2 of GJA8 was found, resulting in synonymous mutation of glycine (GGG) to glycine (GGA). An additional G-->T transvertion at nucleotide 139 (c.139G>T) in exon 2 of GJA8, resulting in a missense mutation of asparagines (GAU) to tyrosine (UAU) at codon 47 (D47Y). These two alterations were not seen in all unaffected members and 100 unrelated control individuals. Bioinformatic analyses also showed that a highly conserved region was located at Asp47. Meanwhile no sequence variations for GJA3 were detected from the 3 affected members.
A novel disease-causing mutation (D47Y) of GJA8 gene in a Chinese family with ADCC is reported.
鉴定常染色体显性遗传性先天性白内障（ADCC）中国家系中缝隙连接蛋白α3/α8基因（GJA3或GJA8）的突变情况。
对所有受试者（5名家庭成员和100名无关对照个体）进行全面眼科检查，从外周血（5 mL）中提取基因组DNA。通过聚合酶链反应（PCR）扩增GJA3/GJA8基因的外显子及其侧翼内含子。纯化后的PCR产物直接测序以筛选致病突变。
双向序列分析发现，GJA8基因第2外显子中第138位核苷酸处发生了G→A转换（c.138G>A），导致甘氨酸（GGG）同义突变为甘氨酸（GGA）。此外，GJA8基因第2外显子中第139位核苷酸处还发生了G→T颠换（c.139G>T），导致第47密码子处天冬酰胺（GAU）错义突变为酪氨酸（UAU）（D47Y）。在所有未患病成员和100名无关对照个体中均未发现这两种改变。生物信息学分析还显示，第47位天冬酰胺位于一个高度保守区域。同时，在3名患病成员中未检测到GJA3的序列变异。
报道了一个ADCC中国家系中GJA8基因的一种新的致病突变（D47Y）。
