Work

A Novel Homozygous Nonsense Pathogenic Variant of the CPAMD8 Gene Associated With Congenital Microcoria

Year: 2025

Type: article

Abstract: Congenital microcoria (MCOR) is a rare inherited ocular disorder. Here, we describe a novel nonsense variant in the CPAMD8 gene in a patient with MCOR. We conducted a comprehensive clinical examination of a patient diagnosed with MCOR and performed whole-exome sequencing to identify potential pathogenic variants. Additionally, bioinformatics prediction tools were employed to assess the impact of the identified variant on protein structure and function. The patient presented with hallmark features of MCOR, such as bilaterally constricted pupils and a poor response to mydriatic agents. A novel homozygous nonsense variant, c.2679C>G (p.Tyr893*), was identified in the CPAMD8 gene. Protein modeling revealed that the variant results in complete truncation of the C-terminal domain of CPAMD8, disrupting its functional domains and potentially affecting its biological activity. Furthermore, electrostatic potential energy analysis demonstrated increased surface asymmetry of the protein, suggesting that the variant may interfere with protein-molecule interactions. Previous studies have suggested a strong association between MCOR and deletions in the 13q32.1 region of chromosome 13; however, the specific pathogenic genes involved have remained unclear. In this study, we show that the nonsense variant c.2679C>G (p.Tyr893*) in CPAMD8 is associated with MCOR, providing new insights into the genetic basis of the disease.

Source: Clinical Genetics

DOI: 10.1111/cge.70067

Authors: Jing‐Fan Gao, Xin Jin, Jing‐Rao Wang, Shu Wang, Hong Zhang

Institutions: Harbin Medical University, First Affiliated Hospital of Harbin Medical University

Language: English

Topic: Ocular Disorders and Treatments

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,980