A Novel Mutation in Mutation Associated with Autosomal Dominant Congenital Cataracts and Microcornea.

Purpose: Crystallin protein mutations are associated with congenital cataract (CC), and several disease-causing mutations in the gene have been identified. We present the location of a new mutation in in members of a Chinese family who presented with CCs with or without microcornea.

Design: Observational study.

Participants: A Chinese family diagnosed with autosomal dominant (AD) CCs with or without microphthalmia.

Methods: Because this was an observational study, it was not registered as a clinical trial. The proband and her 2 children were diagnosed with AD CCs and microcornea and were recruited for the study. Participants underwent complete ophthalmological examinations, and blood samples were used for genomic extraction.

Main Outcome Measures: We detected 1 disease-associated variant using Exomiser analysis by matching the proband's phenotype and the inheritance pattern. The variant was determined to be pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines.

Results: We detected 1 disease-associated variant using Exomiser analysis by matching the proband's phenotype and the inheritance pattern. The variant was determined to be pathogenic according to the American College of Medical Genetics and Genomics guidelines. Next-generation sequencing was verified using Sanger sequencing, and we confirmed that the proband and her children carried the same mutation. We identified the heterozygous variant c.389_390insGCTG (p.C130fs), which includes a frameshift mutation. The residues in p.C130fs are all highly conserved across species. This disease-causing frameshift mutation in the gene is not currently present in the ClinVar database.

Conclusions: Our findings expand the repertoire of known mutations in the gene that cause CCs and provide new insights into the etiology and molecular diagnosis of CCs; however, the molecular mechanism of this mutation warrants further investigation.