Mutations in lens-specific genes: cataract and beyond
作者单位：State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University
会议名称：《中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会》
会议日期：2016年
学科分类：100208[医学-临床检验诊断学] 1002[医学-临床医学] 100212[医学-眼科学] 10[医学]
摘 要：Objective Mutations in lens-specific genes have been frequently reported to play major roles in th e development of congenital cataracts. So far, a number of mutations in these genes have been r eported, including those identified in our patients with cataract. Based on analysis of data from wh ole exome sequencing on 1629 probands with different forms of hereditary eye diseases, a numb ers of novel variants predicted to be damaging were identified. This study aims to clarify the relati onships between different variations in these genes and varied phenotypes in different patients. Method Variations in 32 genes known to cause isolated or primary congenital cataracts were sele cted from the dataset of whole exome sequencing for 1629 probands. After exclusion of polymor phisms and benign variants, rare variants predicted to be damaging were thoroughly analyzed ba sed on existing databases and associated phenotypes. Predicted damaging but unlikely causativ e variants will be summarized. Result Some mutations reported to cause cataracts were detected in patients without cataracts. Some rare damaging variants in these gene may not be causative. Rare variants in some genes are more likely to be pathogenic while such variants in other genes are ambiguous. Classification of these genes and its associated variants are suggested for variants-based genetic counseling. Conclusion Visible clear lens provides valuable model in evaluating effect of a variant on lens str ucture(transparency). Clarifying gene-or variant-specific genotype-phenotype is the prerequisite in making precision genetic counseling. International collaborative studies on such kind of data, pr obably through AEGC or other societies, may be of great help in differentiating rare variants from pathogenic mutations in lens-specific genes responsible for congenital cataracts.