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Mutations in TOP 2B cause autosomal‐dominant hereditary hearing loss via inhibition of the PI 3K‐Akt signalling pathway
Author(s) -
Xia Wenjun,
Hu Jiongjiong,
Ma Jing,
Huang Jianbo,
Jing Tianrui,
Deng Lisha,
Zhang Jin,
Jiang Nan,
Ma Duan,
Ma Zhaoxin
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13482
Subject(s) - exome sequencing , hearing loss , biology , genetics , gene knockdown , protein kinase b , downregulation and upregulation , mutation , gene , exon , hair cell , exome , microbiology and biotechnology , signal transduction , inner ear , medicine , audiology , neuroscience
Hereditary hearing impairment is a clinically and genetically heterogeneous disease. Whole‐exome sequencing was performed on seven affected and six unaffected members in a large Chinese family with autosomal‐dominant nonsyndromic hearing loss. The pathogenic variant of the gene encoding human topoisomerase II β TOP 2B (c.G4837C:p.D1613H) was cosegregated with hearing loss in this pedigree and another two variants of TOP 2B were detected in 66 sporadic patients with hearing loss. top2b knockdown led to significant defects in zebrafish inner ears and caused downregulation of akt which resulted in inactivation of PI 3K‐Akt signalling. As a result, supporting cell and hair cell numbers were reduced through inhibition of the PI 3K‐Akt pathway. Therefore, we hypothesized that mutations in TOP 2B can cause autosomal‐dominant nonsyndromic hearing impairment through inhibition of the PI 3K‐Akt signalling pathway. Database The whole‐exome sequence data in the study are available at the Sequence Read Archive database (NCBI) under the accession numbers SRR9050868 , SRR9050867 , SRR90508676 , SRR90508675 , SRR90508674 , SRR90508673 , SRR90508672 , SRR90508671 , SRR90508679 , SRR90508670 , SRR9050859 . SRR9050858 and SRR9050857 , respectively.