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Title
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A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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The American journal of human genetics / American Society of Human Genetics [Bethesda, Md] - New York, N.Y., 1949, currens
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Publication
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New York, N.Y.
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2012
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ISSN
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0002-9297
[print]
1537-6605
[online]
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DOI
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10.1016/J.AJHG.2012.08.018
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Volume/pages
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91
:4
(2012)
, p. 636-645
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ISI
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000309568500006
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Full text (Publisher's DOI)
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Full text (open access)
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