Li Bin, Lu Bin, Guo Xuewen, Hu Shenghui, Zhao Guihu, Huang Weihong, Hu Jianzhong, Song Kun
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Mobile Health Ministry of Education-China Mobile Joint Laboratory, Xiangya Hospital, Central South University, Changsha, China.
J Ophthalmol. 2020 Feb 19;2020:7054315. doi: 10.1155/2020/7054315. eCollection 2020.
To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. . A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function.
The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.
We report a novel mutation, p.C505S, and a known mutation, p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of p.C505S with iris coloboma has been demonstrated, although p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract. c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.
筛选出一个患有先天性白内障和虹膜缺损的中国家系中的致病基因。招募了一个来自汉族的患有先天性白内障和虹膜缺损的三代家系。从该家系所有个体采集的外周血样本中提取DNA。对先证者采用全外显子测序筛选致病基因突变，对家系中的其他成员以及500名健康个体组成的对照组采用Sanger测序。利用生物信息学分析和三维结构预测来预测氨基酸变化对蛋白质结构和功能的影响。
成功筛选出白内障和虹膜缺损的候选基因。鉴定出一个杂合突变c.70C>A（p.P24T），其与先天性白内障共分离，而另一个此前未报道的杂合突变c.1514G>C（p.C505S）与先天性虹膜缺损共分离。生物信息学分析和三维结构预测证明，此前未报道的c.1514G>C（p.C505S）与先天性虹膜缺损共分离。生物信息学分析和三维结构预测证明，c.70C>A（p.P24T）被鉴定为与先天性白内障共分离，而另一个杂合突变。
我们报告了一个新的突变p.C505S和一个已知突变p.P24T，它们分别与一个中国家系中的虹膜缺损和先天性白内障共分离。这是首次证明p.C505S与虹膜缺损有关联，尽管p.P24T已被广泛报道与先天性白内障有关，尤其是在东亚人群中。这些发现可能对虹膜缺损和先天性白内障的诊断具有未来的治疗益处。这些结果也可能与旨在研究虹膜缺损和先天性白内障分子发病机制的进一步研究相关。此前未报道的c.1514G>C（p.C505S）与先天性虹膜缺损共分离。生物信息学分析和三维结构预测证明，c.70C>A（p.P24T）被鉴定为与先天性白内障共分离，而另一个杂合突变，此前未报道的c.1514G>C（p.C505S）与先天性虹膜缺损共分离。生物信息学分析和三维结构预测证明，c.70C>A（p.P24T）被鉴定为与先天性白内障共分离，而另一个杂合突变。
