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COCH-related autosomal dominant nonsyndromic hearing loss: a phenotype-genotype study

Authors
 Kyung Seok Oh  ;  Daniel Walls  ;  Sun Young Joo  ;  Jung Ah Kim  ;  Jee Eun Yoo  ;  Young Ik Koh  ;  Da Hye Kim  ;  John Hoon Rim  ;  Hye Ji Choi  ;  Hye-Youn Kim  ;  Seyoung Yu  ;  Richard J Smith  ;  Jae Young Choi  ;  Heon Yung Gee  ;  Jinsei Jung 
Citation
 HUMAN GENETICS, Vol.141(3-4) : 889-901, 2022-04 
Journal Title
HUMAN GENETICS
ISSN
 0340-6717 
Issue Date
2022-04
MeSH
Arthrogryposis ; Deafness* / genetics ; Extracellular Matrix Proteins / genetics ; Genotype ; Hearing Loss* / genetics ; Hearing Loss, Sensorineural* / genetics ; Humans ; Mutation ; Pedigree ; Phenotype
Abstract
This phenotype-genotype study aimed to investigate the extent of audioprofile variability related to cochlin major domains and to identify potential ethnic-specific differences associated with COCH-related hearing loss. Eight Korean families (26 cases) were diagnosed with COCH-related hearing loss by exome sequencing. Audiometric test results were combined with those from nine published East Asian families (20 cases) and compared with those from 38 European-descent families (277 cases). Audioprofiles were created by grouping audiometric test results into age ranges by age at testing and then averaging hearing loss thresholds by frequency within age ranges. The functional impact of the identified variants was assessed in vitro by examining the intracellular trafficking, secretion, and cleavage of cochlin. In both East Asian and European-descent families segregating COCH-related hearing loss, deafness-associated variants in non-LCCL domains of cochlin were associated with hearing loss that was more severe earlier in life than hearing loss caused by variants in the LCCL domain. Consistent with this phenotypic difference, functional studies demonstrated distinct pathogenic mechanisms for COCH variants in a domain-dependent manner; specifically, a cytotoxic effect was observed for the p.Phe230Leu variant, which is located in the vWFA1 domain. No ethnic-specific differences in hearing loss progression were observed, except for those attributable to an overrepresentation of presymptomatic cases in the European-descent cohort.
Full Text
https://link.springer.com/article/10.1007/s00439-021-02368-y
DOI
10.1007/s00439-021-02368-y
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hye-Youn(김혜연) ORCID logo https://orcid.org/0000-0003-2090-6427
Rim, John Hoon(임정훈) ORCID logo https://orcid.org/0000-0001-6825-8479
Jung, Jinsei(정진세) ORCID logo https://orcid.org/0000-0003-1906-6969
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
Choi, Jae Young(최재영) ORCID logo https://orcid.org/0000-0001-9493-3458
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191351
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