Case Report: Identification of a CRYGD variant in a family with congenital cataract

Congenital cataract is an important cause of childhood visual impairment, and genetic factors contribute substantially to its etiology. We report a boy aged 4–5 years with congenital cataract from a family with an apparent autosomal dominant inheritance pattern. Comprehensive ophthalmic examinations were performed in the proband and available relatives. Whole-exome sequencing (WES) in the proband identified several candidate variants, including a heterozygous CRYGD c.391T>C (p.Trp131Arg) variant. Subsequent Sanger sequencing was used to validate the candidate variants and assess segregation in available family members. The CRYGD c.391T>C (p.Trp131Arg) variant was present in all tested affected family members and absent in the tested unaffected relative, supporting co-segregation with the disease phenotype in this pedigree. Additional variants identified by WES, including ITM2B c.537C>G (p.Asn179Lys) and ASB10 c.1402T>C (p.Ter468GlnextTer6), showed segregation patterns that were less consistent with the familial phenotype. According to ACMG criteria, the CRYGD variant remained classified as a variant of uncertain significance. To provide limited biological context, we also reviewed a public gene expression dataset and found lens-enriched expression of CRYGD , consistent with its established role in lens biology. This case may provide useful evidence for future variant interpretation and genetic counseling in congenital cataract families carrying CRYGD variants; however, further functional studies are required to clarify the pathogenic significance of c.391T>C (p.Trp131Arg).