目的:单侧感音神经性听力损失(USNHL)是耳鼻喉科临床中常见的一种病症。然而,其分子发病机制尚不清楚。本研究旨在调查儿童USNHL的遗传基础,并分析相关的听力学特征。
方法:前瞻性招募队列的回顾性分析。
方法:三级转诊中心。
方法:我们在2018年1月1日至2021年12月31日之间招募了38名患有USNHL的儿童,并进行了身体,听力学,成像,和先天性巨细胞病毒(cCMV)检查以及使用针对30个耳聋基因的下一代测序(NGS)进行的基因检测。比较了不同病因的听力学结果。
结果:在8例(21.1%)患者中发现了致病性遗传变异,包括5个GJB2变体,2与PAX3变体,和1与EDNRB变体。在各种听力图结构中发现GJB2变异与轻度至中度USNHL相关,而PAX3和EDNRB变异体在平坦听力图构型中与深度USNHL相关。此外,在2个与常染色体隐性遗传相容的多重家族中,我们进行了针对213个耳聋基因的全基因组测序和延伸NGS;但尚未发现明确的致病变异.耳蜗神经缺损和cCMV感染分别为9例和2例,没有明确基因诊断的患者。
结论:遗传基础可以导致大约20%的儿童USNHL,不同的基因型与不同的听力学特征有关。这些发现强调了基因检查在指导诊断中的实用性,咨询,以及儿童USNHL的治疗。
Unilateral sensorineural hearing loss (USNHL) is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood USNHL and analyze the associated audiological features.
Retrospective analysis of a prospectively recruited cohort.
Tertiary referral center.
We enrolled 38 children with USNHL between January 1, 2018, and December 31, 2021, and performed physical, audiological, imaging, and congenital cytomegalovirus (cCMV) examinations as well as genetic testing using next-generation sequencing (NGS) targeting 30 deafness genes. The audiological results were compared across different etiologies.
Causative genetic variants were identified in 8 (21.1%) patients, including 5 with GJB2 variants, 2 with
PAX3 variants, and 1 with the EDNRB variant. GJB2 variants were found to be associated with mild-to-moderate USNHL in various audiogram configurations, whereas
PAX3 and EDNRB variants were associated with profound USNHL in flat audiogram configurations. In addition, whole-genome sequencing and extended NGS targeting 213 deafness genes were performed in 2 multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and cCMV infection were observed in 9 and 2, respectively, patients without definite genetic diagnoses.
Genetic underpinnings can contribute to approximately 20% of childhood USNHL, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of USNHL in children.