Genetic spectrum of congenital cataract with optional ocular and multisystem abnormalities

To identify disease-causing gene variants in 114 probands with congenital cataract (CC), either isolated or accompanied by additional ocular abnormalities and multisystem disorders.

A total of 114 probands with CC who accept cataract surgery between 2021 and 2022 were enrolled. All probands and available family members underwent a comprehensive ophthalmologic examinations and received clinical diagnoses. Medical history and examination data were collected. Whole-exome sequencing (WES) was performed for all probands, and candidate variants were further validated by co-segregation analysis.

Among 114 probands, 49 presented with isolated CC, and 11 exhibited CC combined with systemic abnormalities such as congenital heart disease (CHD), laryngeal cartilage hypoplasia and developmental delay, the remaining were associated with congenital ocular anomalies including iris hypoplasia, posterior capsular defect, microcornea, and microphthalmia. In total, 49 variants were identified across 19 genes, 23 of which were novel. The detection rate of variants by WES was substantially higher in inherited families (68.75%, 11/16) than in sporadic cases (38.78%, 38/98), with an overall detection rate of 42.98% (49/114).

This study provided a comprehensive characterization of the diverse clinical phenotypes of CC in Chinese cohort and updates the mutational landscape of CC-associated genes. By employing WES, we expand the genetic spectrum and highlight additional genotype-phenotype correlations in CCs.