ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy.

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 a de novo variant, p.E818K of ATP1A3, 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 of ATP1A3 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, the de 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.

• Authors: Kyu-Hee Han, Doo-Yi Oh, Seungmin Lee, Chung Lee, Jin Hee Han, Min Young Kim, Hye-Rim Park, Moo Kyun Park, Nayoung K D Kim, Jaekwang Lee, Eunyoung Yi, Jong-Min Kim, Jeong-Whun Kim, Jong-Hee Chae, Seung Ha Oh, Woong-Yang Park, Byung Yoon Choi
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 16504 (11 28 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 29184165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP1A3 protein, human
• Sodium-Potassium-Exchanging ATPase

Topics

• Adolescent
• Adult
• Child
• Cochlear Implantation
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genetic Testing
• Genotype
• Hearing Loss, Central (diagnosis, genetics, physiopathology, therapy)
• Humans
• Male
• Middle Aged
• Multimodal Imaging (methods)
• Mutation
• Pedigree
• Phenotype
• Polymorphism, Single Nucleotide
• Sodium-Potassium-Exchanging ATPase (genetics)
• Treatment Outcome
• Exome Sequencing
• Young Adult