Yang Zhenfei, Li Qian, Ma Xu, Zhu Si Quan
a Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Eye Center , Beijing Tongren Hospital, Capital Medical University , Beijing , China .
b Graduate School, Peking Union Medical College , Beijing , China .
Curr Eye Res. 2015;40(12):1225-31. doi: 10.3109/02713683.2014.997885. Epub 2014 Dec 30.
To identify the molecular basis and clinical phenotype in three Chinese families with hereditary cataracts.
Detailed family history and clinical data were recorded. The phenotypes were documented using slit-lamp photography. Candidate genes sequencing was performed to screen out the disease causing mutation. Bioinformatics analysis was performed to predict the function of mutant genes.
The phenotypes of the families were identified as nuclear cataract in Family 1, pulverulent cataract in Family 2, and nuclear cataract in Family 3. Direct sequencing revealed transversions of C > T at c.218 (p. S73F) in GJA8 in Family 1, A > C at c.125 (p. E42A) in GJA3 in Family 2, and C > T at c.268 (p. L90F) in GJA3 in Family 3. These mutations co-segregated with all affected individuals in the family and were not found in unaffected family members nor in the 100 unrelated controls. Bioinformatics analysis indicated that S73F in GJA8, E42A and L90F in GJA3 are highly conserved. S73F in GJA8, E42A and L90F in GJA3 could possibly be damaging predicted by PolyPhen-2, with score of 0.858, 1.000, 1.000, respectively.
This study identified three mutations in three Chinese families with hereditary cataracts. Of the three mutations, two were novel (c.125 A > C in GJA3 and c.268 C > T in GJA3), one was previously reported (c.218 C > T in GJA8).
确定三个患有遗传性白内障的中国家系的分子基础和临床表型。
记录详细的家族史和临床数据。使用裂隙灯摄影记录表型。进行候选基因测序以筛选出致病突变。进行生物信息学分析以预测突变基因的功能。
家系1的表型被鉴定为核性白内障，家系2为粉末状白内障，家系3为核性白内障。直接测序显示，家系1中GJA8基因c.218处的C>T颠换（p.S73F），家系2中GJA3基因c.125处的A>C颠换（p.E42A），家系3中GJA3基因c.268处的C>T颠换（p.L90F）。这些突变与家族中所有受影响个体共分离，在未受影响的家族成员和100名无关对照中均未发现。生物信息学分析表明，GJA8中的S73F、GJA3中的E42A和L90F高度保守。通过PolyPhen-2预测，GJA8中的S73F、GJA3中的E42A和L90F可能具有破坏性，得分分别为0.858、1.000、1.000。
本研究在三个患有遗传性白内障的中国家系中鉴定出三个突变。在这三个突变中，两个是新发现的（GJA3基因c.125 A>C和GJA3基因c.268 C>T），一个是先前报道过的（GJA8基因c.218 C>T）。
