Elbagoury Nagham M, Ashaat Engy A, Mekkawy Mona K, Mohamed Ragaey Y, Askoura Anas M, Milad Peter M, Essawi Mona L
Department of Medical Molecular Genetics, National Research Centre, Giza, 12311, Egypt.
Department of Clinical Genetics, National R esearch Centre, Giza, Egypt.
Eur J Pediatr. 2025 Mar 18;184(4):257. doi: 10.1007/s00431-025-06052-5.
Hearing loss (HL) is an impending disorder. The high incidence of congenital genetic HL affects the language and communication skills of a large number of children worldwide. Our study is mainly concerned with exploring the genetic etiology of congenital hearing loss through Sanger sequencing of the coding exon in GJB2, the most common causative gene worldwide, in 17 patients from 13 unrelated families followed by whole exome sequencing for cases showing biallelic wildtype GJB2. Eleven patients from eight families showed homozygous and compound heterozygous variants in the GJB2 gene. Six patients from five families proceeded to whole exome sequencing. One of them showed a reported variant in ILDR1, and three showed novel variants in the TMC1 and KCNQ1 genes. Two showed variants reported for the first time in HL patients in the PEX6 and MYO3A genes.In conclusion, this study suggests new insights into the contribution of MYO3A, KCNQ1, and PEX6 to congenital sensorineural hearing loss as well as possible expansion of the phenotypic spectrum of the TMC1 gene. What is Known: • Sanger sequencing and whole exome sequencing are used for molecular diagnosis of syndromic and non-syndromic types of hearing loss (HL). • TMC1 gene causes a type of non-syndromic HL. What is New: • Expanding the molecular spectrum of MYO3A, PEX6, TMC1, and KCNQ1 genes as contributor genes in HL by detecting variants first time to be detected in HL patients. • Expanding the clinical spectrum of TMC1 gene to cause syndromic and non-syndromic HL.
听力损失（HL）是一种常见疾病。先天性遗传性HL的高发病率影响着全球大量儿童的语言和沟通能力。我们的研究主要关注通过对13个无亲缘关系家庭的17名患者中全球最常见致病基因GJB2的编码外显子进行桑格测序来探索先天性听力损失的遗传病因，对于显示GJB2双等位基因野生型的病例随后进行全外显子测序。来自8个家庭的11名患者在GJB2基因中显示纯合和复合杂合变异。来自5个家庭的6名患者进行了全外显子测序。其中1名患者在ILDR1中显示一个已报道的变异，3名患者在TMC1和KCNQ1基因中显示新变异。2名患者在PEX6和MYO3A基因中显示首次在HL患者中报道的变异。总之，本研究为MYO3A、KCNQ1和PEX6对先天性感音神经性听力损失的作用提供了新见解，以及TMC1基因表型谱可能的扩展。已知信息：• 桑格测序和全外显子测序用于综合征型和非综合征型听力损失（HL）的分子诊断。• TMC1基因导致一种非综合征型HL。新发现：• 通过检测首次在HL患者中检测到的变异，扩大了MYO3A、PEX6、TMC1和KCNQ1基因作为HL致病基因的分子谱。• 扩大了TMC1基因导致综合征型和非综合征型HL的临床谱。
