Damrongchietanon Tasyakorn, Wattanasirichaigoon Duangrurdee, Khongkraparn Arthaporn, Noojarern Saisuda, Tiravanitchakul Rattinan, Kasemkosin Nittaya, Kiatthanabumrung Sivaporn, Tim-Aroon Thipwimol, Wongkittichote Parith
Division of Medical Genetics, Department of Pediatrics, Mahidol University, Bangkok, Thailand.
Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand.
Sci Rep. 2025 Sep 25;15(1):32784. doi: 10.1038/s41598-025-18038-2.
Prelingual sensorineural hearing loss (SNHL) represents about 80% of genetic SNHL, with at least 90 causative genes identified. In order to identify the genetic diagnosis of prelingual SNHL, we performed a prospective study by systematic history-taking and phenotyping, followed by whole-exome sequencing (WES) with target gene analysis in 100 Thai patients. We found an overall diagnostic yield of 46%, 58.3% for familial cases, and 39.0% for sporadic cases. These included 41 cases with nonsyndromic SNHL(nsSNHL) and 5 cases with syndromic SNHL (sSNHL). We identified 41 P/LP and 4 VUS variants of 15 genes. Of those sSNHL, the causative genes were PAX3, SOX10, MITF (Waardenburg and Teitz syndromes), and SLC26A4 (Pendred syndrome). The genetic defects identified among those with nsSNHL were GJB2 and SLC26A4 as the most prevalent causes, followed by MYO15A, MYO7A, POU3F4, OTOF, PCDH15, GSDME, PTEN, ACTG1, TMPRSS3, MITF, and MPZL2. The inheritance of these nsSNHL genes involved X-linked recessive (n = 3), autosomal dominant (n = 3), and autosomal recessive in the remainder (n = 36). Patients with positive mutations underwent surveillance for associated symptoms like goiter and retinitis pigmentosa. In conclusion, most prelingual SNHL was nsSNHL with autosomal recessive inheritance. Identifying the causative gene benefits patients for specific management and genetic counseling.
语前感音神经性听力损失（SNHL）约占遗传性SNHL的80%，已确定至少90个致病基因。为了明确语前SNHL的基因诊断，我们对100例泰国患者进行了一项前瞻性研究，通过系统的病史采集和表型分析，随后进行全外显子测序（WES）及目标基因分析。我们发现总体诊断率为46%，家族性病例为58.3%，散发性病例为39.0%。其中包括41例非综合征性SNHL（nsSNHL）和5例综合征性SNHL（sSNHL）。我们鉴定出15个基因的41个致病性/可能致病性（P/LP）变异和4个意义未明的变异（VUS）。在那些sSNHL病例中，致病基因是PAX3、SOX10、MITF（瓦登伯革综合征和泰茨综合征）以及SLC26A4（彭德莱德综合征）。在nsSNHL患者中鉴定出的基因缺陷以GJB2和SLC26A4最为常见，其次是MYO15A、MYO7A、POU3F4、OTOF、PCDH15、GSDME、PTEN、ACTG1、TMPRSS3、MITF和MPZL2。这些nsSNHL基因的遗传方式包括X连锁隐性遗传（n = 3）、常染色体显性遗传（n = 3），其余为常染色体隐性遗传（n = 36）。发生阳性突变的患者接受了甲状腺肿和视网膜色素变性等相关症状的监测。总之，大多数语前SNHL为常染色体隐性遗传的nsSNHL。确定致病基因有助于患者进行针对性管理和遗传咨询。
