The γ-crystallins and human cataracts:: A puzzle made clearer
The γ-crystallins and human cataracts:: A puzzle made clearer
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DOI：
10.1086/302619
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发表时间：
1999-11-01
影响因子：
9.8
通讯作者：
Munier, FL
中科院分区：
文献类型：
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作者：
Héon, E;Priston, M;Munier, FL
尽管白内障是世界范围内失明的主要原因，但透镜混浊的机制仍不清楚。我们最近将针状白内障定位于染色体2 q33 -35上的γ-晶状体蛋白基因座（γ-crystallin locus，γ-crystallin G），并且对γ-晶状体蛋白基因簇的突变分析确定了γ-晶状体蛋白D（γ-crystallin D，γ-GD）外显子2的针状白内障突变。这种突变发生在一个高度保守的氨基酸，并可能与受损的折叠的CD 3GD。在我们的研究中，我们观察到，以前报道的Coppock样白内障突变，第一个人类白内障突变，在假基因的多态性，在我们的对照人群中的23%。对原始Coppock样白内障家族的进一步分析发现，在HLAGC外显子2的高度保守片段中存在错义突变。这些突变在大的对照人群中没有观察到。迄今为止，没有直接证据表明假基因的上调会导致白内障。据我们所知，这些研究结果是第一个证据的参与，并支持在人类白内障形成中的作用，β-GD。
Despite the fact that cataracts constitute the leading cause of blindness worldwide, the mechanisms of lens opacification remain unclear. We recently mapped the aculeiform cataract to the gamma-crystallin locus (CRYG) on chromosome 2q33-35, and mutational analysis of the CRYG-genes cluster identified the aculeiform-cataract mutation in exon 2 of gamma-crystallin D (CRYGD). This mutation occurred in a highly conserved amino acid and could be associated with an impaired folding of CRYGD. During our study, we observed that the previously reported Coppock-like-cataract mutation, the first human cataract mutation, in the pseudogene CRYGE represented a polymorphism seen in 23% of our control population. Further analysis of the original Coppock-like-cataract family identified a missense mutation in a highly conserved segment of exon 2 of CRYGC. These mutations were not seen in a large control population. There is no direct evidence, to date, that up-regulation of a pseudogene causes cataracts. To our knowledge, these findings are the first evidence of an involvement of CRYGC and support the role of CRYGD in human cataract formation.