A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-Recessive Hearing Impairment
2012 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-Recessive Hearing Impairment
Schrauwen, I.; Helfmann, S.; Inagaki, A.; Predoehl, F. ; Tabatabaiefar, M. A.; Picher, M. M. & Sommen, M. et al. (2012)
American journal of human genetics, 91(4) pp. 636-645. DOI: https://doi.org/10.1016/j.ajhg.2012.08.018
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Details
- Authors
- Schrauwen, Isabelle; Helfmann, Sarah; Inagaki, Akira; Predoehl, Friederike ; Tabatabaiefar, Mohammad Amin; Picher, Maria Magdalena ; Sommen, Manou; Seco, Celia Zazo; Oostrik, Jaap; Kremer, Hannie; Dheedene, A.; Claes, Charlotte; Fransen, Erik; Chaleshtori, Morteza Hashemzadeh; Coucke, Paul; Lee, Amy; Moser, Tobias ; Camp, Guy van
- Abstract
- CaBPs are a family of Ca2+-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 Ca2+ signaling through effectors such as voltage-gated Ca-v Ca2+ channels. In this study, we identified a splice-site mutation (c.637+1G>T) in Ca2+-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(star)4). Compared with wild-type CaBP2, the truncated CaBP2 showed altered Ca2+ binding in isothermal titration calorimetry and less potent regulation of Ca(v)1.3 Ca2+ channels. We show that genetic defects in CABP2 cause moderate-to-severe sensorineural hearing impairment. The mutation might cause a hypofunctional CaBP2 defective in Ca2+ sensing and effector regulation in the inner ear.
- Issue Date
- 2012
- Publisher
- Cell Press
- Journal
- American journal of human genetics
- ISSN
- 0002-9297