ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy
| Autor: | Jong Hee Chae, Min Young Kim, Woong-Yang Park, Jin Hee Han, Doo Yi Oh, Seungmin Lee, Byung Yoon Choi, Jeong Whun Kim, Nayoung K.D. Kim, Eunyoung Yi, Kyu Hee Han, Jaekwang Lee, Hye Rim Park, Chung Lee, Seung Ha Oh, Jong Min Kim, Moo Kyun Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Proband medicine.medical_specialty Adolescent Genotype Hearing loss lcsh:Medicine Audiology Multimodal Imaging Polymorphism Single Nucleotide Article Young Adult 03 medical and health sciences 0302 clinical medicine Atrophy ATP1A3 Exome Sequencing medicine otorhinolaryngologic diseases Humans Genetic Predisposition to Disease Genetic Testing Hearing Loss Central Child lcsh:Science Genetic Association Studies Exome sequencing Multidisciplinary Cerebellar ataxia business.industry lcsh:R Middle Aged medicine.disease Cochlear Implantation Pedigree Phenotype Treatment Outcome 030104 developmental biology Mutation Female Sensorineural hearing loss Synaptopathy lcsh:Q Sodium-Potassium-Exchanging ATPase medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) Scientific Reports SCIENTIFIC REPORTS(7) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-16676-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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