Abstract

Background Genetic variants are the leading cause of congenital cataract (CC). To date, numerous genes have been implicated in the development of CC. The objective of the present study was to report two previously unrecognized gene variants associated with CC in two unrelated Chinese families, identified through whole exome sequencing (WES). Methods Two unrelated Chinese families affected by CC were recruited. Cytogenetic and molecular genetic analyses were performed using karyotyping, chromosomal microarray analysis (CMA), and WES. In addition, RNA sequencing was conducted to assess differentially expressed genes in affected individuals compared with healthy controls. Results Karyotype and CMA elicited none of chromosome abnormalities in both of the families. However, WES revealed a novel missense variant NM_006891.4:c.154 T > C(p.S52P) in the CRYGD gene in the proband of Family 1, which was inherited from her mother with CC. In Family 2, a novel frameshift variant NM_000276.4:c.1046dup(p.M349Ifs∗36) in the OCRL gene was identified in the fetus via WES, which was inherited from the mother who had CC. RNA sequencing further demonstrated significantly reduced OCRL mRNA expression in the fetus compared with age-matched controls. Conclusion The present study reports, for the first time, two novel variants in CRYGD and OCRL that were identified in the Chinese families with CC. These findings may expand the mutational spectrum of CC and highlight the utility of WES for the genetic diagnosis of patients with CC.