Journal Article
Clinical and genetic architecture of a large cohort with auditory neuropathy
Hongyang Wang; Liping Guan; Xiaonan Wu; Jing Guan; Jin Li; Nan Li; Kaili Wu; Ya Gao; Dan Bing; Jianguo Zhang; Lan Lan; Tao Shi; Danyang Li; Wenjia Wang; Linyi Xie; Fen Xiong; Wei Shi; Lijian Zhao; Dayong Wang; Ye Yin; Qiuju Wang
Human Genetics · Vol. 143, Issue 3 · pp. 293-309 · 2024
Abstract
Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1 , is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.