PUBLICATION
Mutations in TOP2B cause autosomal-dominant hereditary hearing loss via inhibition of the PI3K-Akt signalling pathway
- Authors
- Xia, W., Hu, J., Ma, J., Huang, J., Jing, T., Deng, L., Zhang, J., Jiang, N., Ma, D., Ma, Z.
- ID
- ZDB-PUB-190615-9
- Date
- 2019
- Source
- FEBS letters 593(15): 2008-2018 (Journal)
- Registered Authors
- Keywords
- PI3K-Akt signalling pathway, TOP2B, deafness genes, non-syndromic hearing loss, zebrafish
- MeSH Terms
-
- Animals
- DNA Topoisomerases, Type II/genetics*
- Exome Sequencing/methods*
- Female
- Gene Knockdown Techniques
- Genetic Association Studies
- Genetic Predisposition to Disease
- Hair Cells, Auditory/metabolism
- Hearing Loss, Sensorineural/genetics*
- Humans
- Male
- Pedigree
- Phosphatidylinositol 3-Kinases/metabolism
- Point Mutation*
- Poly-ADP-Ribose Binding Proteins/genetics*
- Proto-Oncogene Proteins c-akt/metabolism
- Signal Transduction*
- Zebrafish
- PubMed
- 31198993 Full text @ FEBS Lett.
Citation
Xia, W., Hu, J., Ma, J., Huang, J., Jing, T., Deng, L., Zhang, J., Jiang, N., Ma, D., Ma, Z. (2019) Mutations in TOP2B cause autosomal-dominant hereditary hearing loss via inhibition of the PI3K-Akt signalling pathway. FEBS letters. 593(15):2008-2018.
Abstract
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 non-syndromic hearing loss. The pathogenic variant of the gene encoding human topoisomerase IIβ TOP2B (c.G4837C:p.D1613H) was co-segregated with hearing loss in this pedigree and another two variants of TOP2B 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 PI3K-Akt signalling. As a result, supporting-cell and hair-cell numbers were reduced through inhibition of the PI3K-Akt pathway. Therefore, we hypothesised that mutations in TOP2B can cause autosomal-dominant non-syndromic hearing impairment through inhibition of the PI3K-Akt signalling pathway. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping