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).