Eye Center of the 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou, China.
Hum Mutat. 2011 Dec;32(12):1367-70. doi: 10.1002/humu.21552. Epub 2011 Sep 9.
Congenital cataract (CC) is the leading cause of visual disability in children. To date, mutations in many genes have been linked to CC. In a four-generation Chinese family with congenital nuclear pulverulent and posterior polar cataracts, we detected a heterozygous c.5G>A transition in the second exon of GJA3, resulting in the substitution of a highly conserved glycine with aspartic acid (p.G2D) at the N-terminus of the connexin46 (Cx46) protein. Wild type (wt) and mutant Cx46 plasmids were transfected into HeLa cells to examine the molecular basis of cataract formation. Unlike wt Cx46, Cx46G2D mutant formed gap junction plaques inefficiently, changed hemichannel permeability, and caused apoptosis. These results suggest that the glycine residue at the second position of the N-terminus is important for gap junction plaque formation and hemichannel function.
先天性白内障（CC）是儿童视力障碍的主要原因。迄今为止，许多基因的突变都与 CC 有关。在一个四代同堂的中国家庭中，有先天性核性粉末状和后极性白内障，我们在 GJA3 的第二个外显子中检测到杂合 c.5G>A 转换，导致连接蛋白 46（Cx46）蛋白的 N 端高度保守的甘氨酸被天冬氨酸取代（p.G2D）。将野生型（wt）和突变型 Cx46 质粒转染到 HeLa 细胞中，以研究白内障形成的分子基础。与 wt Cx46 不同，Cx46G2D 突变体形成缝隙连接斑块效率低下，改变半通道通透性，并导致细胞凋亡。这些结果表明，N 端第二位的甘氨酸残基对于缝隙连接斑块形成和半通道功能很重要。
