title: A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment.
abstract: 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.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schrauwen
authors.forename: Sarah
authors.initials: S
authors.lastname: Helfmann
authors.forename: Akira
authors.initials: A
authors.lastname: Inagaki
authors.forename: Friederike
authors.initials: F
authors.lastname: Predoehl
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Tabatabaiefar
authors.forename: Maria Magdalena
authors.initials: MM
authors.lastname: Picher
authors.forename: Manou
authors.initials: M
authors.lastname: Sommen
authors.forename: Celia
authors.initials: C
authors.lastname: Zazo Seco
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostrik
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
authors.forename: Annelies
authors.initials: A
authors.lastname: Dheedene
authors.forename: Charlotte
authors.initials: C
authors.lastname: Claes
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Morteza Hashemzadeh
authors.initials: MH
authors.lastname: Chaleshtori
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics*; D025063:Chromosome Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003051:Cochlea / Q000378:metabolism / Q000503:physiopathology*; D003241:Consanguinity; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D057809:HEK293 Cells; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D002135:Calcium-Binding Proteins; C085578:Ca-binding protein 2; D002118:Calcium