He Wei, Li Xin, Chen Jiajing, Xu Ling, Zhang Feng, Dai Qiushi, Cui Hao, Wang Duen-Mei, Yu Jun, Hu Songnian, Lu Shan
Shenyang He Eye Hospital, He College of Ophthalmology and Visual Science, Shenyang, China.
Ophthalmic Genet. 2011 Mar;32(1):48-53. doi: 10.3109/13816810.2010.535886. Epub 2010 Dec 21.
The aim of the study was to characterize the underlying mutation in a large multiplex Chinese family with hereditary nuclear cataract.
A 6-generation Chinese family having hereditary nuclear cataract was recruited and clinically verified. Blood DNA samples were obtained from 53 available family members. Linkage analyses were performed on the known candidate regions for hereditary cataract with 36 polymorphic microsatellite markers. To identify mutations related to cataract, a direct sequencing approach was applied to a candidate gene residing in our linkage locus.
A linkage locus was identified with a maximum 2-point LOD score of 4.31 (recombination fraction = 0) at marker D1S498 and a maximum multipoint LOD score of 5.7 between markers D1S2344 and D1S498 on chromosome 1q21.1, where the candidate gene Cx50 is located. Direct sequencing of Cx50 showed a 139 G to A transition occurred in all affected family members. This transitional mutation resulted in a replacement of aspartic acid by asparagine at residue 47 (D47N) and led to a loss-of-function of the protein.
The D47N mutation of Cx50 causes the hereditary nuclear cataract in this family in an autosomal dominant mode of inheritance with incomplete penetrance.
本研究旨在明确一个患有遗传性核性白内障的中国大家族潜在的突变情况。
招募了一个具有遗传性核性白内障的6代中国家族并进行临床确诊。从53名可获取血样的家族成员中采集血液DNA样本。运用36个多态性微卫星标记对遗传性白内障的已知候选区域进行连锁分析。为鉴定与白内障相关的突变，对位于我们连锁定位区域的一个候选基因采用直接测序法。
在1号染色体1q21.1区域，于标记D1S498处鉴定出一个连锁位点，其两点最大LOD值为4.31（重组率 = 0），在标记D1S2344和D1S498之间多点最大LOD值为5.7，候选基因Cx50位于该区域。对Cx50进行直接测序显示，所有患病家族成员均发生了139G→A的转换。这种转换突变导致第47位氨基酸由天冬氨酸替换为天冬酰胺（D47N），并致使该蛋白质功能丧失。
Cx50基因的D47N突变以常染色体显性遗传且外显不全的方式导致了该家族的遗传性核性白内障。
