Purpose Congenital cataract (CC) is a significant cause of lifelong visual loss. Its genetic diagnosis is challenging due to marked genetic heterogeneity. The purpose of this article is to report the genetic findings in sporadic and familial CC patients.Methods Patients (n=54) who were clinically diagnosed with CC and their parents were recruited. Blood samples were collected in our hospital. Mutations were detected by high-throughput, next-generation DNA sequencing (NGS) targeting 792 genes frequently involved in common inherited eye diseases.Results We identified variants in 11/38 cases (28.95%) of sporadic CC and 14/16 cases (87.5%) of familial CC, indicating a significant difference (P=0.000). Of the 14 variants identified in sporadic cases, 9 were previously reported mutations, and 5 were novel mutations, including 2 de novo mutations (CRYBB2 c.487C>T, FYCO1c.215A>T). The most frequent variants in our cohort were in crystallins and cytoskeletal genes (7/30, 23.33%), followed by X-linked syndromic proteins (13.33%) and transcriptional factors (10.00%). Additional information on the possibility of complications with inherited ocular or systemic diseases other than CC was provided in 20/30 (66.67%) variants.Conclusions These results contribute to expanding the mutation spectrum and frequency. Targeted NGS in CC provided significant diagnostic information and enabled more accurate genetic counseling. This study reports the different distributions of mutation genes in familial and sporadic CC cases.