PDF(Pubmed)
Abstract：
Congenital cataract (CC), the most prevalent cause of childhood blindness and amblyopia, necessitates prompt and precise genetic diagnosis. The objective of this study is to identify the underlying genetic cause in a Swiss patient with isolated CC. Whole exome sequencing (WES) and copy number variation (CNV) analysis were conducted for variant identification in a patient born with a total binocular CC without a family history of CC. Sanger Sequencing was used to confirm the variant and segregation analysis was used to screen the non-affected parents. The first de novo missense mutation at c.391T>C was identified in exon 3 of CRYGC on chromosome 2 causing the substitution of a highly conserved Tryptophan to an Arginine located at p.Trp131Arg. Previous studies exhibit significant changes in the tertiary structure of the crystallin family in the following variant locus, making CRYGC prone to aggregation aggravated by photodamage resulting in cataract. The variant can be classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria (PP3 + PM1 + PM2 + PS2; scoring 10 points). The identification of this novel variant expands the existing knowledge on the range of variants found in the CRYGC gene and contributes to a better comprehension of cataract heterogeneity.
摘要：
先天性白内障（CC），儿童失明和弱视的最普遍原因，需要迅速和精确的基因诊断。这项研究的目的是确定患有孤立CC的瑞士患者的潜在遗传原因。进行全外显子组测序（WES）和拷贝数变异（CNV）分析，以在没有CC家族史的患有总双眼CC的患者中进行变体鉴定。Sanger测序用于确认变体,并且分离分析用于筛选未受影响的亲本。在2号染色体CRYGC的外显子3中鉴定出c.391T>C处的第一个从头错义突变，导致高度保守的色氨酸取代为位于p.Trp131Arg的精氨酸。先前的研究显示以下变异基因座中晶状体蛋白家族的三级结构发生了显着变化，使CRYGC容易聚集加重光损伤导致白内障。根据美国医学遗传学和基因组学学院(ACMG)标准(PP3+PM1+PM2+PS2;得分10分),该变体可被分类为致病性的。这种新变体的鉴定扩展了对CRYGC基因中发现的变体范围的现有知识，并有助于更好地理解白内障异质性。
