Congenital coralliform cataract is the predominant consequence of a recurrent mutation in the CRYGD gene

Abstract

Background Congenital cataract is a leading cause of treatable childhood blindness and both clinically and genetically heterogeneous. Among the already characterized phenotypes, coralliform cataract is a rare special form of congenital cataracts. Although previous studies had shown that mutations in the γD-crystallin (CRYGD) can result in congenital coralliform cataracts, no conclusive genotype-phenotype correlation might be drawn. Here we aimed to identify the spectrum and frequency of CRYGD gene mutations in congenital coralliform cataracts of Chinese origin. Methods The medical records of 392 Chinese families with congenital cataracts were reviewed between January 2011 and December 2021. The families, clinically documented to have congenital coralliform cataracts, were screened for mutations in candidate CRYGD gene. The genomic DNA of all subjects was extracted from peripheral blood leukocytes. PCR amplified and direct sequencing were performed to identify the disease-causing mutation. Results A total of 12 families with coralliform cataracts were recruited in this study in the past 10 years, accounting for 3.1% of the families with congenital cataracts. Of the 12 families, all affected individuals presented with bilateral non-progressive coralliform cataracts since birth, with the best-corrected Snellen visual acuities ranging from 20/200 to 20/25. A recurrent c.70 C > A (p. P24T) mutation in CRYGD was identified in 10 families (83.3%) with congenital cataract, which co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched normal controls. Conclusions The coralliform cataract is characterized by being bilateral, non-progressive and present at birth. A recurrent p.P24T CRYGD mutation occurs independently in 83.3% of the Chinese families with congenital coralliform cataracts and most likely represents a mutational hot spot, which underscore the relations between coralliform cataract and p.P24T CRYGD.

Improving the Yield of Genetic Diagnosis through Additional Genetic Panel Testing in Hereditary Ophthalmic Diseases

“…The solubility and stability of γD-crystallin are essential for maintaining lens transparency. Mutations in the CRYGD gene may compromise the solubility and stability of crystallin proteins, thereby reducing lens transparency and leading to congenital cataracts [40]. In case yx9 with AD POAG caused by MYOC, the findings from numerous empirical studies corroborate the assertion that a gain-of-function mechanism plays a role in the pathogenesis of myocilin-associated glaucoma [41].…”