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*
  • 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*
  • Whole Exome Sequencing/methods*
  • Zebrafish
PubMed
31198993 Full text @ FEBS Lett.
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
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes