PUBLICATION

A missense mutation in DCDC2 causes human recessive deafness DFNB66, likely by interfering with sensory hair cell and supporting cell cilia length regulation

Authors
Grati, M., Chakchouk, I., Ma, Q., Bensaid, M., DeSmidt, A., Turki, N., Yan, D., Baanannou, A., Mittal, R., Driss, N., Blanton, S., Farooq, A., Lu, Z., Liu, X.Z., Masmoudi, S.
ID
ZDB-PUB-150121-4
Date
2015
Source
Human molecular genetics   24(9): 2482-91 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chromosome Mapping
  • Cilia/metabolism*
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Genes, Recessive*
  • Genes, Reporter
  • Hair Cells, Auditory/metabolism*
  • Hearing Loss, Sensorineural/genetics*
  • Homozygote
  • Humans
  • Male
  • Microtubule-Associated Proteins/genetics*
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree
  • Sequence Alignment
  • Zebrafish
PubMed
25601850 Full text @ Hum. Mol. Genet.
Abstract
Hearing loss is the most common sensory deficit in humans. We show that a point mutation in DCDC2 (DCDC2a), a member of doublecortin domain-containing protein superfamily, causes nonsyndromic recessive deafness DFNB66 in a Tunisian family. Using immunofluorescence on rat inner ear neuroepithelia, DCDC2a was found to localize to the kinocilia of sensory hair cells and the primary cilia of nonsensory supporting cells. DCDC2a fluorescence is distributed along the length of the kinocilium with increased density toward the tip. DCDC2a-GFP overexpression in non-polarized COS7 cells induces the formation of long microtubule-based cytosolic cables suggesting a role in microtubule formation and stabilization. Deafness mutant DCDC2a expression in hair cells and supporting cells causes cilium structural defects, such as cilium branching, and up to a three-fold increase in length ratios. In zebrafish, the ortholog dcdc2b was found to be essential for hair cell development, survival, and function. Our results reveal DCDC2a to be a deafness gene and a player in hair cell kinocilia and supporting cell primary cilia length regulation likely via its role in microtubule formation and stabilization.
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