Jiang Lan, Xu Hongen, Liu Danhua, Zhang Sen, Xu Ying
Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Children's Hospital of Zhengzhou University/Henan Children's Hospital/Zhengzhou Children's Hospital, Zhengzhou, China.
Precision Medicine Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Front Pediatr. 2022 Nov 15;10:1005335. doi: 10.3389/fped.2022.1005335. eCollection 2022.
Auditory neuropathy (AN) is a hearing disorder caused by the failure of inner hair cells, auditory nerve synapses and/or auditory nerves. With the development of high-throughput sequencing technology, the genetic factors of AN have been revealed, and genetic testing has become an important tool for identifying different types of AN.
To study the genetic cause of nonsyndromic auditory neuropathy in a Chinese family. The family was from Henan Province with three affected individuals. The audiological examinations were performed on the affected individuals, and whole-exome sequencing was carried out on the proband. The suspected pathogenic variants screened by the bioinformatic analysis were validated using Sanger sequencing in the family members. We identified three novel variants c.3277G > A (.Glu1093Lys), c.4024-4G > T, and c.898-2A > G of the gene in the three children with AN. The first two variants were inherited from their father, and the third variant was inherited from their mother. A minigene assay was designed to test the effect of c.4024-4G > T on splicing. The variants c.3277G > A, c.4024-4G > T, and c.898-2A > G could be classified as likely pathogenic/pathogenic following the ACMG guidelines, and they are considered as the genetic causes for the patients in the family.
New pathogenic/likely pathogenic variants of the gene were identified in a family with AN, enriching the mutational spectrum of the gene.
听觉神经病（AN）是一种由内毛细胞、听觉神经突触和/或听觉神经功能障碍引起的听力障碍。随着高通量测序技术的发展，AN的遗传因素已被揭示，基因检测已成为识别不同类型AN的重要工具。
为研究一个中国家庭中非综合征性听觉神经病的遗传原因。该家庭来自河南省，有三名患者。对患者进行了听力学检查，并对先证者进行了全外显子组测序。通过生物信息学分析筛选出的疑似致病变异，在家庭成员中使用桑格测序进行验证。我们在三名患有AN的儿童中鉴定出该基因的三个新变异：c.3277G＞A（.Glu1093Lys）、c.4024-4G＞T和c.898-2A＞G。前两个变异来自他们的父亲，第三个变异来自他们的母亲。设计了一个小基因检测来测试c.4024-4G＞T对剪接的影响。根据美国医学遗传学与基因组学学会（ACMG）指南，变异c.3277G＞A、c.4024-4G＞T和c.898-2A＞G可被分类为可能致病/致病，它们被认为是该家庭患者的遗传原因。
在一个患有AN的家庭中鉴定出该基因的新的致病/可能致病变异，丰富了该基因的突变谱。
