ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Han, Kyu-Hee; Oh, Doo-Yi; Lee, Seungmin; Lee, Chung; Han, Jin Hee; Kim, Min Young; Park, Hye-Rim; Park, Moo Kyun; Kim, Nayoung; Lee, Jaekwang; Yi, Eunyoung; Kim, Jong-Min; Kim, Jeong-Whun; Chae, Jong-Hee; Oh, Seung Ha; Park, Woong-Yang; Choi, Byung Yoon
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 11
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-16676-9
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract The etiologies and prevalence of sporadic, postlingual-onset, progressive auditory neuropathy spectrum disorder (ANSD) have rarely been documented. Thus, we aimed to evaluate the prevalence and molecular etiologies of these cases. Three out of 106 sporadic progressive hearing losses turned out to manifest ANSD. Through whole exome sequencing and subsequent bioinformatics analysis, two out of the three were found to share ade novo variant, p.E818K ofATP1A3, which had been reported to cause exclusively CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome. However, hearing loss induced by CAPOS has never been characterized to date. Interestingly, the first proband did not manifest any features of CAPOS, except subclinical areflexia; however, the phenotypes of second proband was compatible with that of CAPOS, making this the first reported CAPOS allele in Koreans. This ANSD phenotype was compatible with known expression ofATP1A3 mainly in the synapse between afferent nerve and inner hair cells. Based on this, cochlear implantation (CI) was performed in the first proband, leading to remarkable benefits. Collectively, thede novo ATP1A3 variant can cause postlingual-onset auditory synaptopathy, making this gene a significant contributor to sporadic progressive ANSD and a biomarker ensuring favorable short-term CI outcomes.