PUBLICATION

New role of LRP5, associated with non-syndromic autosomal recessive hereditary hearing loss

Authors
Xia, W., Hu, J., Liu, F., Ma, J., Sun, S., Zhang, J., Jin, K., Huang, J., Jiang, N., Wang, X., Li, W., Ma, Z., Ma, D.
ID
ZDB-PUB-170706-7
Date
2017
Source
Human Mutation   38(10): 1421-1431 (Journal)
Registered Authors
Wang, Xu
Keywords
Hereditary hearing loss, LRP5, Non syndromic hearing loss, Wnt signaling pathway
MeSH Terms
  • Animals
  • Cell Proliferation/genetics
  • Disease Models, Animal
  • Ear, Inner/pathology*
  • Female
  • Gene Knockdown Techniques
  • Hair Cells, Auditory/pathology*
  • Hearing Loss, Sensorineural/genetics*
  • Hearing Loss, Sensorineural/physiopathology
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5/genetics*
  • Male
  • Morpholinos/genetics
  • Mutation
  • Pedigree
  • Whole Exome Sequencing
  • Wnt Signaling Pathway/genetics
  • Zebrafish/genetics
PubMed
28677207 Full text @ Hum. Mutat.
Abstract
Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. And at least 50% of hearing loss are due to a genetic etiology. Although hundreds of genes have been reported, there were still hundreds of related deafness genes to be found. Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with post-lingual non-syndromic sensorineural hearing loss. Whole-exome sequencing identified lipoprotein receptor-related protein 5 (LRP5), a member of the low-density lipoprotein receptor family, as the causative gene in this family. In the zebrafish model, lrp5 downregulation using morpholinos led to significant abnormalities in zebrafish inner ear and lateral line neuromasts and contributed, to some extent, to disabilities in hearing and balance. Rescue experiments showed that LRP5 mutation is associated with hearing loss. Knocking down lrp5 in zebrafish results in reduced expression of several genes linked to Wnt signaling pathway and decreased cell proliferation when compared with those in wild type zebrafish. In conclusion, the LRP5 mutation influences cell proliferation through the Wnt signaling pathway, thereby reducing the number of supporting cells and hair cells and leading to non-syndromic hearing loss in this Chinese family. 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
This article is corrected by ZDB-PUB-220906-108 .