Elmakhzen Badreddine, Rollier Paul, Saillard Clémence, Godey Benoit, Le Marechal Cédric, Gueguen Paul, Fajardy Isabelle, Odent Sylvie, Pasquier Laurent
Service de Génétique Clinique, Centre de Référence CLAD-Ouest, ERN ITHACA, CHU, Rennes, France.
Service de génétique et oncogénétique, CHU HASSAN 2, Fès, Morocco.
Mol Genet Genomic Med. 2025 May;13(5):e2474. doi: 10.1002/mgg3.2474.
GJB2 and GJB6 variants, encoding Cx26 and Cx30 respectively, are the most frequently involved genes commonly contributing to hereditary hearing loss either isolated or in combination with skin abnormalities. GJB6 variations are classically associated with two distinct conditions: non-syndromic hearing loss and hidrotic ectodermal dysplasia, type Clouston, the latter typically not involving deafness.
Whole genome sequencing (WGS) was used to find genetic variants after clinical features of a 13-year-old female patient were recorded.
In this report, we describe the association of congenital hearing loss and ectodermal anomalies (palmoplantar keratoderma, knuckle pads, and nail dystrophy) in a female with the ENST00000647029.1 (GJB6): c.175G>A (p.(Gly59Arg)) GJB6 variant. As a result, we report on the third case of individuals showing this same missense variant and syndromic hearing loss.
This study underscores the overlapping phenotypes observed in patients with the p.Gly59Arg variant in the GJB6 gene. The findings suggest a continuum of phenotypic presentations for this variant, with the key clinical features being the combination of congenital hearing loss and hyperkeratosis.
GJB2和GJB6基因变异分别编码Cx26和Cx30，是导致遗传性听力损失最常见的相关基因，可单独或与皮肤异常共同出现。GJB6变异经典地与两种不同情况相关：非综合征性听力损失和Clouston型汗孔角化性外胚层发育不良，后者通常不涉及耳聋。
在记录一名13岁女性患者的临床特征后，使用全基因组测序（WGS）来寻找基因变异。
在本报告中，我们描述了一名女性患者中先天性听力损失与外胚层异常（掌跖角化病、指节垫和甲营养不良）与ENST00000647029.1（GJB6）：c.175G>A（p.(Gly59Arg)) GJB6变异之间的关联。因此，我们报告了第三例显示相同错义变异和综合征性听力损失的个体。
本研究强调了在GJB6基因中携带p.Gly59Arg变异的患者中观察到的重叠表型。研究结果表明该变异存在一系列表型表现，关键临床特征是先天性听力损失和角化过度的组合。
