GJB2基因纯合变异作为Waardenburg综合征潜在拟表型的病例报告

文献信息

中文摘要

背景： Waardenburg综合征（WS）是一种神经嵴病，主要特征为先天性听力损失和多系统色素异常。方法：我们报告一名12岁汉族女孩，表现为中重度感音神经性听力损失、鼻根宽、毛发弥漫性色素减退和面部雀斑——这些特征部分类似于WS表型。然而，其计算的W指数为1.87，低于内眦异位（dystopia canthorum）的诊断阈值（>1.95），且其整体临床表现不符合任何WS亚型的诊断标准。全外显子组测序（WES）及随后的家系Sanger测序在先证者中鉴定出GJB2纯合变异c.109G > A（p.Val37Ile），父母双方均被证实为杂合携带者。结果：基于综合的临床和遗传学证据，该患者被诊断为GJB2相关常染色体隐性非综合征性听力损失（DFNB1A）。其类WS特征被解释为可能的拟表型。结论：本病例强调，对于表现出不完全或不典型WS特征的听力损失患者，全面的基因检测——包括GJB2分析——对于鉴别拟表型、确定准确病因以及为精准诊断和遗传咨询提供依据至关重要。

英文摘要

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.