A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment

Am J Hum Genet. 2012 Oct 5;91(4):636-45. doi: 10.1016/j.ajhg.2012.08.018. Epub 2012 Sep 13.


CaBPs are a family of Ca(2+)-binding proteins related to calmodulin and are localized in the brain and sensory organs, including the retina and cochlea. Although their physiological roles are not yet fully elucidated, CaBPs modulate Ca(2+) signaling through effectors such as voltage-gated Ca(v) Ca(2+) channels. In this study, we identified a splice-site mutation (c.637+1G>T) in Ca(2+)-binding protein 2 (CABP2) in three consanguineous Iranian families affected by moderate-to-severe hearing loss. This mutation, most likely a founder mutation, probably leads to skipping of exon 6 and premature truncation of the protein (p.Phe164Serfs(∗)4). Compared with wild-type CaBP2, the truncated CaBP2 showed altered Ca(2+) binding in isothermal titration calorimetry and less potent regulation of Ca(v)1.3 Ca(2+) channels. We show that genetic defects in CABP2 cause moderate-to-severe sensorineural hearing impairment. The mutation might cause a hypofunctional CaBP2 defective in Ca(2+) sensing and effector regulation in the inner ear.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calcium-Binding Proteins / genetics*
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / metabolism
  • Chromosome Disorders / physiopathology
  • Cochlea / metabolism
  • Cochlea / physiopathology*
  • Consanguinity
  • Exons / genetics
  • Female
  • Genes, Recessive
  • Genetic Predisposition to Disease
  • HEK293 Cells
  • Hair Cells, Auditory / metabolism
  • Hair Cells, Auditory / pathology*
  • Hair Cells, Auditory / physiology*
  • Hearing Loss / genetics*
  • Hearing Loss / metabolism
  • Hearing Loss / physiopathology
  • Humans
  • Male
  • Mutation*
  • Pedigree


  • Calcium-Binding Proteins
  • Ca-binding protein 2
  • Calcium