Case Report: A family of congenital cataract caused by a novel mutation in the CRYGC gene c.52G>A.

BACKGROUND: Congenital cataract refers to lens opacity present at birth or progressively developing in the neonatal period, caused by inherited genetic abnormalities or developmental disorders. The etiology of congenital cataract is multifactorial, and its exact pathogenesis remains incompletely understood. Generally, it can be broadly categorized into genetic factors and non-genetic factors (including environmental influences, intrauterine infections or complications during delivery). This case report presents a hereditary congenital cataract characterized by classical clinical manifestations, high penetrance, and a novel pathogenic gene mutation site that has not been previously documented in medical literature. We herein report this unique case to enhance our understanding of congenital cataract pathogenesis and expand the mutational spectrum associated with this ocular disorder.

CASE PRESENTATION: A 30-year-old female presented with blurred vision in her left eye since childhood. Slit-lamp microscopy revealed len opacity in the left eye. Based on the patient's age of onset, ocular examination findings, and family history, the diagnosis of congenital cataract was established. Multiple family members had been previously diagnosed with "bilateral congenital cataracts." Following cataract surgery, the patient's visual acuity in the left eye improved to 20/40. To investigate the genetic etiology in this pedigree, whole-exome sequencing was performed on peripheral venous blood samples after obtaining informed consent from the patient and her family. Genetic testing identified a heterozygous missense mutation in exon 2 of the CRYGC gene (c.52G>A:p. Glu18Lys). This mutation results in the substitution of a highly conserved glutamic acid residue with lysine at position 18. Notably, this genetic variant was absent in unaffected family members.

CONCLUSION: The patients in this pedigree exhibited an autosomal dominant inheritance pattern, with all affected individuals presenting bilateral lens opacities unaccompanied by systemic abnormalities, confirming a definitive diagnosis of congenital cataracts. Genetic screening identified a novel CRYGC gene mutation (c.52G>A:p. Glu18Lys) as the pathogenic cause of congenital cataracts in this family. Our findings expand the mutational spectrum of the CRYGC gene associated with congenital cataracts and provide enhanced insights into the molecular basis of this condition.