A homozygous variant in the GJB2 gene as a potential phenocopy of Waardenburg syndrome: case report.
- 1Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology, Ganzhou, Jiangxi, China.
- 2The First Clinical Medical College, Gannan Medical University, Ganzhou, Jiangxi, China.
Abstract
Waardenburg syndrome (WS) is a neurocristopathy primarily characterized by congenital hearing loss and multisystem pigmentary abnormalities. We report a 12-year-old Han Chinese girl who presented with moderate-to-severe sensorineural hearing loss, a wide nasal root, diffuse hypopigmentation of the hair, and facial freckles-features partially similar to the WS phenotype. However, her calculated W-index was 1.87, below the diagnostic threshold for dystopia canthorum (>1.95), and her overall clinical presentation did not meet the diagnostic criteria for any WS subtype. Whole-exome sequencing (WES) and subsequent familial Sanger sequencing identified a homozygous GJB2 variant, c.109G > A (p.Val37Ile), in the proband, with both parents confirmed as heterozygous carriers. Based on the integrated clinical and genetic evidence, the patient was diagnosed with GJB2-related autosomal recessive nonsyndromic hearing loss (DFNB1A). Her WS-like features were interpreted as a possible phenocopy. This case highlights that in patients with hearing loss exhibiting incomplete or atypical WS features, comprehensive genetic testing-including analysis of GJB2-is crucial to differentiate phenocopies, establish an accurate etiology, and provide a basis for precise diagnosis and genetic counseling.
Related
- Cockayne Syndrome Phenotype in a Sudanese Child With a Homozygous ERCC8 Splice-Site Variant of Uncertain Significance: A Case Report
- Case Report: Genetic and functional analysis of a novel homozygous intronic CD46 variant in a patient with atypical hemolytic uremic syndrome
- A Novel Homozygous Variant Associated With Distinct Clinical Phenotypes of SDR9C7 Nonsyndromic Epidermal Differentiation Disorder in Two Affected Patients From a Consanguineous Saudi Family
- Characterization of a novel homozygous CTLA4 variant.
- Multi-omics approach to map a clinically diverse large cohort with homozygous founder RAG1 p.C176F variant among Old Order Mennonites
BibTeX
@article{wu2026homozygous,
title = {{A homozygous variant in the GJB2 gene as a potential phenocopy of Waardenburg syndrome: case report.}},
author = {Yuehua Wu and Yupeng Chen and Zimeng Guo and Lang Xie and Tao Yang and Longnian Li},
journal = {Frontiers in medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1925409},
url = {https://europepmc.org/article/MED/42908807},
note = {CC BY},
}
RIS
TY - JOUR
TI - A homozygous variant in the GJB2 gene as a potential phenocopy of Waardenburg syndrome: case report.
AU - Yuehua Wu
AU - Yupeng Chen
AU - Zimeng Guo
AU - Lang Xie
AU - Tao Yang
AU - Longnian Li
PY - 2026
DA - 2026/10/07
JO - Frontiers in medicine
DO - 10.3389/fmed.2026.1925409
UR - https://europepmc.org/article/MED/42908807
AB - Waardenburg syndrome (WS) is a neurocristopathy primarily characterized by congenital hearing loss and multisystem pigmentary abnormalities. We report a 12-year-old Han Chinese girl who presented with moderate-to-severe sensorineural hearing loss, a wide nasal root, diffuse hypopigmentation of the hair, and facial freckles-features partially similar to the WS phenotype. However, her calculated W-index was 1.87, below the diagnostic threshold for dystopia canthorum (>1.95), and her overall clinical presentation did not meet the diagnostic criteria for any WS subtype. Whole-exome sequencing (WES) and subsequent familial Sanger sequencing identified a homozygous GJB2 variant, c.109G > A (p.Val37Ile), in the proband, with both parents confirmed as heterozygous carriers. Based on the integrated clinical and genetic evidence, the patient was diagnosed with GJB2-related autosomal recessive nonsyndromic hearing loss (DFNB1A). Her WS-like features were interpreted as a possible phenocopy. This case highlights that in patients with hearing loss exhibiting incomplete or atypical WS features, comprehensive genetic testing-including analysis of GJB2-is crucial to differentiate phenocopies, establish an accurate etiology, and provide a basis for precise diagnosis and genetic counseling.
SN - 2296-858X
ER -