期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms242316594
关键词
congenital cataract; CRYGC; crystallin; whole exome sequencing; conserved tryptophan; UV damage
This study identified a novel missense mutation in the CRYGC gene as the underlying genetic cause of isolated congenital cataract in a Swiss patient. The mutation in exon 3 resulted in the substitution of a highly conserved tryptophan residue, leading to cataract formation. The findings contribute to a better understanding of the genetic heterogeneity of cataract.
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.
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