Case Report: A Novel Mutation in the CRYGD Gene Causing Congenital Cataract Associated with Nystagmus in a Chinese Family.

Purpose: Congenital cataract (CC) is a common disease resulting in leukocoria and the leading cause of blindness in children worldwide. Approximately 50% of congenital cataract is inherited. Our aim is to identify mutations in a Chinese family with congenital cataract. Methods: A four-generation Chinese family diagnosed with congenital cataract was recruited in West China Hospital of Sichuan University. Genomic DNA was extracted from the peripheral blood of these participants. All coding exons and flanking regions were amplified and sequenced, and the variants were validated using Sanger sequencing. AlphaFold2 was used to predict possible protein structural changes in this variant. Results: The proband had congenital nuclear cataract with nystagmus. A heterozygous variant c.233C > T was identified in exon 2 of the CRYGD gene in chromosome 2. This mutation resulted in a substitution of serine with phenylalanine at amino acid residue 78 (p.S78F). The variant might result in a less stable structure with a looser loop and broken hydrogen bond predicted by AlphaFold2, and this mutation was co-segregated with the disease phenotype in this family. Conclusion: We described cases of human congenital cataract caused by a novel mutation in the CRYGD gene and provided evidence of further phenotypic heterogeneity associated with this variant. Our study further extends the mutation spectrum of the CRYGD gene in congenital cataract.

A mutated CRYGD associated with congenital coralliform cataracts in two Chinese pedigrees.

AIM: To investigate the causal gene mutation and clinical characteristics for two Chinese families with autosomal dominant congenital coralliform cataract. METHODS: Two Chinese pedigrees with congenital cataract were investigated. Routine ophthalmic examinations were performed on all patients and non-affected family members. Peripheral blood samples were collected, and the genomic DNAs were extracted. The coding regions of proband's DNAs were analyzed with cataract gene panel. The identified mutation was amplified by polymerase chain reaction, and automated sequencing was performed in other members of two families to verify whether the mutated gene was co-segregated with the disease. RESULTS: Congenital coralliform cataract was inherited in an autosomal dominant mode in both pedigrees. For each family, more than half of the family members were affected. All patients presented with severe visual impairment after birth as a result of bilateral symmetric coralliform lens opacification. An exact the same defect in the same gene, a heterozygous mutation of c.70C>A (p. P24T) in exon 2 of γD-crystallin gene, was detected in both probands from each family. Sanger sequencing analysis demonstrated that the mutated CRYGD was co-segregated in these two families. CONCLUSION: A c.70C>A (p. P24T) variant in CRYGD gene was reconfirmed to be the causal gene in two Chinese pedigrees. It is known that mutated CRYGD caused most of the congenital coralliform cataracts, suggesting that the CRYGD gene is associated with coralliform congenital cataract.