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.
Picher MM, Gehrt A, Meese S, Ivanovic A, Predoehl F, Jung S, Schrauwen I, Dragonetti AG, Colombo R, Van Camp G, Strenzke N, Moser T.Picher MM, et al.Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):E1717-E1726. doi: 10.1073/pnas.1617533114. Epub 2017 Feb 9.Proc Natl Acad Sci U S A. 2017.PMID: 28183797Free PMC article.
Yang T, Scholl ES, Pan N, Fritzsch B, Haeseleer F, Lee A.Yang T, et al.PLoS One. 2016 Jan 25;11(1):e0147495. doi: 10.1371/journal.pone.0147495. eCollection 2016.PLoS One. 2016.PMID: 26809054Free PMC article.
Ortner NJ, Pinggera A, Hofer NT, Siller A, Brandt N, Raffeiner A, Vilusic K, Lang I, Blum K, Obermair GJ, Stefan E, Engel J, Striessnig J.Ortner NJ, et al.Pflugers Arch. 2020 Jan;472(1):3-25. doi: 10.1007/s00424-019-02338-4. Epub 2019 Dec 17.Pflugers Arch. 2020.PMID: 31848688Free PMC article.
Koohiyan M, Reiisi S, Azadegan-Dehkordi F, Salehi M, Abtahi H, Hashemzadeh-Chaleshtori M, Noori-Daloii MR, Tabatabaiefar MA.Koohiyan M, et al.Iran J Public Health. 2019 Sep;48(9):1704-1713.Iran J Public Health. 2019.PMID: 31700827Free PMC article.