Rare KCNQ4 variants found in public databases underlie impaired channel activity that may contribute to hearing impairment
| Autor: | Seyoung Yu, Ji Hyun Lee, Min Goo Lee, Joon Suk Lee, John Hoon Rim, Haiyue Lin, Jae Young Choi, Heon Yung Gee, Jinsei Jung, Hyunsoo Jin, Wan Namkung, Hye Youn Kim, Hye Ji Choi, Young Ik Koh, Kunhi Ryu, Hak Joon Lee |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry lcsh:Medicine Deafness medicine.disease_cause computer.software_genre Biochemistry 0302 clinical medicine Gene Frequency Hearing Cricetinae Databases Genetic Missense mutation lcsh:QD415-436 Mutation education.field_of_study KCNQ Potassium Channels Database Potassium channel activity Mechanisms of disease 030220 oncology & carcinogenesis Molecular Medicine medicine.symptom Ion Channel Gating KCNQ4 Hearing loss Population Neurophysiology CHO Cells Biology Article lcsh:Biochemistry 03 medical and health sciences Cricetulus otorhinolaryngologic diseases medicine Animals Humans Genetic variation Hearing Loss education Molecular Biology Allele frequency Public Sector lcsh:R Minor allele frequency HEK293 Cells 030104 developmental biology computer |
| Zdroj: | Experimental and Molecular Medicine, Vol 51, Iss 8, Pp 1-12 (2019) Experimental & Molecular Medicine |
| ISSN: | 2092-6413 1226-3613 |
| Popis: | KCNQ4 is frequently mutated in autosomal dominant non-syndromic hearing loss (NSHL), a typically late-onset, initially high-frequency loss that progresses over time (DFNA2). Most KCNQ4 mutations linked to hearing loss are clustered around the pore region of the protein and lead to loss of KCNQ4-mediated potassium currents. To understand the contribution of KCNQ4 variants to NSHL, we surveyed public databases and found 17 loss-of-function and six missense KCNQ4 variants affecting amino acids around the pore region. The missense variants have not been reported as pathogenic and are present at a low frequency (minor allele frequency Deafness: Missed mutations raise risk of hearing loss A gene associated with hereditary hearing loss may play a greater role than previously recognized in age-related auditory impairment. Many cases of autosomal dominant non-syndromic hearing loss (ADNSHL) arise from defects in KCNQ4, a protein that maintains the cellular ionic conditions needed for normal inner ear function. Researchers led by Heon Yung Gee and Jae Young Choi at Yonsei University College of Medicine, Seoul, South Korea, have now uncovered numerous previously overlooked mutations in the gene encoding KCNQ4 that may also contribute to adult-onset hearing loss. Their survey of human genome databases revealed 23 additional sequence variants that can meaningfully impair function of this protein. The effects of some of these mutations can be at least partially corrected with existing chemical compounds, indicating the potential to protect a subset of ADNSHL patients from future deafness. |
| Databáze: | OpenAIRE |
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