PUBLICATION

SLC44A4 Mutation Causes Autosomal Dominant Hereditary Postlingual Non-syndromic Mid-frequency Hearing loss

Authors
Ma, Z., Xia, W., Liu, F., Ma, J., Sun, S., Zhang, J., Jiang, N., Wang, X., Hu, J., Ma, D.
ID
ZDB-PUB-161226-1
Date
2017
Source
Human molecular genetics   26(2): 383-394 (Journal)
Registered Authors
Wang, Xu
Keywords
acetylcholine, mutation, choline, genes, auditory hair cell, outer auditory hair cells, sensorineural hearing loss, inner ear, zebrafish, genetics, acoustics, nerve supply, hearing impairment, whole exome sequencing
MeSH Terms
  • Animals
  • Asians
  • Ear, Inner/physiopathology*
  • Exome/genetics
  • Genetic Association Studies
  • Hair Cells, Auditory/pathology
  • Hearing Loss/genetics*
  • Hearing Loss/physiopathology
  • Hearing Loss, Sensorineural/genetics*
  • Hearing Loss, Sensorineural/physiopathology
  • Humans
  • Membrane Transport Proteins/genetics*
  • Morpholinos
  • Mutation
  • Pedigree
  • Zebrafish/genetics
  • Zebrafish/growth & development
PubMed
28013291 Full text @ Hum. Mol. Genet.
Abstract
Clinical, genetic, and functional investigations were performed to identify the causative mutation in a distinctive Chinese family with postlingual non-syndromic mid-frequency sensorineural hearing loss. Whole-exome sequencing revealed SLC44A4, which encodes the choline transport protein, as the pathogenic gene in this family. In the zebrafish model, downregulation of slc44a4 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. SH-SY5Y cells transfected with SLC44A4 showed higher choline uptake and acetylcholine release than that of cells transfected with mutant SLC44A4 We concluded that mutation of SLC44A4 may cause defects in the Choline- acetylcholine system, which is crucial to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury, leading to hearing loss.
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-220906-80 .