Huang X, Wang N, Xiao X, Li S, Zhang Q
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Eye (Lond). 2015 Jul;29(7):972-7. doi: 10.1038/eye.2015.74. Epub 2015 May 15.
To identify genetic defects in a large family with open angle glaucoma (OAG) and microcornea.
Genomic 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.
Exome 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.
A 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.
确定一个患有开角型青光眼（OAG）和小角膜的大家族中的基因缺陷。
从一个中国家族三代的15名个体的白细胞中提取基因组DNA，其中包括7名患有OAG和小角膜的个体、1名单纯小角膜个体以及7名健康个体。对先证者的基因组DNA进行全外显子组测序。通过多步骤生物信息学分析获得候选变异，并通过桑格测序和分离分析进行验证。
外显子组测序在GJA1中检测到一个候选变异，即一个新的截短突变（c.791_792delAA，p.K264Ifs*43）。该突变存在于所有7名患有OAG和小角膜的个体以及1名单纯小角膜个体中，但在该家族的7名未受影响的亲属中不存在。在505名无青光眼的无关对照的1394个等位基因和192名正常对照中均未发现该突变。8名个体中有7名未观察到眼外体征；只有1名个体患有牙釉质发育不全和并指畸形。
GJA1中的一个新的截短突变与一个中国家族中的OAG和小角膜相关。这表明GJA1应被纳入青光眼的候选基因。
