Genome sequencing reveals novel variants in a diverse population with congenital anterior segment anomalies

Sci Rep. 2025 Jan 2;15(1):518. doi: 10.1038/s41598-024-84205-6.

Abstract

Congenital anterior segment anomalies are disorders that affect the development of the eye and cause severe visual impairment. The molecular basis of congenital anterior segment anomalies is not well known. In this study, genome sequencing was performed on 27 families from diverse ethnicities with congenital anterior segment anomalies and 11 variants were identified, most of which were novel and family specific. These variants included single nucleotide variants CPAMD8:c.4825 C > T, c.534 G > A, CRYBB1:c.683 C > A, NHS:c.1180 C > T, GJA3:c.176 C > T, CRYGC:c.470 G > A, COL2A1:c.2819 G > A, c.1693 C > T, EPHA2:c.2864 A > C, a splice donor variant in COL11A1:c.933 + 1del, and a copy number variant in FBN1. The observed inheritance patterns were predominantly dominant, with a few recessive cases and a single instance of X-linked inheritance. Genome sequencing identified variants in 40.74% of diverse cases, offering valuable insights for enhancing the diagnosis and management of this disorder.

Keywords: Anterior segment anomaly; Cataract; Congenital; Ethnicities; Genome sequencing; Glaucoma.

MeSH terms

  • Adipokines
  • Adult
  • Anterior Eye Segment* / abnormalities
  • Child
  • Collagen Type XI / genetics
  • DNA Copy Number Variations
  • Eye Abnormalities / genetics
  • Female
  • Fibrillin-1 / genetics
  • Humans
  • Male
  • Mutation
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Whole Genome Sequencing

Substances

  • Collagen Type XI
  • FBN1 protein, human
  • COL11A1 protein, human
  • Fibrillin-1
  • Adipokines