A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family
A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family
复制标题
一个新的 GJA1 截短突变与一个中国大家庭的开角型青光眼和小角膜相关
作者：
Huang, X.;Wang, N.;Zhang, Q.
目的对一个中国人开角型青光眼（OAG）伴小角膜大家系的遗传缺陷进行鉴定。方法从一个中国人开角型青光眼（OAG）伴小角膜大家系（7例OAG伴小角膜大家系，1例单纯小角膜大家系，7例健康人）的白细胞中提取基因组DNA。对先证者的基因组DNA进行全外显子组测序。通过多步生物信息学分析获得候选变异体，并通过桑格测序和分离分析进行验证。791_792delAA，第K264Ifs* 43页）。这种突变存在于所有7个OAG和小角膜的个体和单独的小角膜的个体中，但不存在于家族中7个未受影响的亲属中。在505名无青光眼的无关对照和192名正常对照的1394个等位基因中不存在。眼外的迹象没有观察到在七个人，只有一个是受影响的牙釉质发育不全和并指syndactyly.ConclusionsA新的截断突变GJA1与OAG和小角膜在中国家庭。这表明GJA1应该被列为青光眼的候选基因。
PurposeTo identify genetic defects in a large family with open angle glaucoma (OAG) and microcornea.MethodsGenomic DNA was prepared from leukocytes of 15 individuals from three generations of a Chinese family, including seven individuals with OAG and microcornea, one with microcornea alone, and seven healthy individuals. Whole exome sequencing was performed on genomic DNA of the proband. Candidate variants were obtained through multiple steps of bioinformatics analysis and validated by Sanger sequencing and segregation analysis.ResultsExome sequencing detected a candidate variant in GJA1, a novel truncation mutation (c. 791_792delAA, p. K264Ifs* 43). This mutation was present in all seven individuals with OAG and microcornea and the individual with microcornea alone, but not in the seven unaffected relatives in the family. It was not present in 1394 alleles from 505 unrelated controls without glaucoma and 192 normal controls. Extraocular signs were not observed in seven out of the eight individuals; only one was affected with dental enamel hypoplasia and syndactyly.ConclusionsA novel truncation mutation in GJA1 is associated with OAG and microcornea in a Chinese family. This suggests that GJA1 should be included as a candidate gene for glaucoma.