To evaluate the diagnostic yield of congenital ectopia lentis (EL) in a Chinese cohort by combining panel-based next-generation sequencing with clinical findings.

A cohort study.

In total, 175 patients with congenital EL and their available family members (n = 338) were enrolled. All patients with congenital EL underwent genetic testing. Genotype-phenotype analyses were conducted to assess the biometric and structural ocular manifestations of congenital EL.

In total, 175 patients with congenital EL and 338 of their relatives were included in this study. In these patients, 92.57% (162 of 175) of disease-related variants were detected in FBN1 (83.43%), CPAMD8 (1.71%), COL4A5 (0.57%), ADAMTSL4 (3.43%), LTBP2 (1.71%), and CBS (2.29%). Based on genetic and clinical findings, the primary diagnostic rate was increased to 40.57% from 19.43% with the exception of the 91 diagnoses of potential Marfan syndrome, with a new diagnostic strategy for congenital EL, thus having been developed. Within this group of patients harboring FBN1 mutations, 16.44% (19 of 141) probands were diagnosed with EL syndrome and 2.13% (3 of 141) were diagnosed with Marfan syndrome.

The results of this cohort study expand the genomic landscape associated with congenital EL in Chinese cohorts. FBN1 mutations represent the most common cause of congenital EL in this population, and we have developed a new diagnostic strategy for congenital EL subtypes via the use of a well-designed panel-based next-generation sequencing that can be used to efficiently and precisely diagnose patients with congenital EL in a cost-effective manner.