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

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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.
Keywords
CALMODULIN, GENE, NIGHT BLINDNESS, CONGENITAL DEAFNESS, CA2+ CHANNELS, CA(V)1.3 CHANNELS, CA2+-BINDING PROTEINS, CALCIUM-BINDING PROTEINS, IDENTIFICATION, INACTIVATION

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MLA
Schrauwen, Isabelle, Sarah Helfmann, Akira Inagaki, et al. “A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-recessive Hearing Impairment.” AMERICAN JOURNAL OF HUMAN GENETICS 91.4 (2012): 636–645. Print.
APA
Schrauwen, Isabelle, Helfmann, S., Inagaki, A., Predoehl, F., Tabatabaiefar, M. A., Picher, M. M., Sommen, M., et al. (2012). A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment. AMERICAN JOURNAL OF HUMAN GENETICS, 91(4), 636–645.
Chicago author-date
Schrauwen, Isabelle, Sarah Helfmann, Akira Inagaki, Friederike Predoehl, Mohammad Amin Tabatabaiefar, Maria Magdalena Picher, Manou Sommen, et al. 2012. “A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-recessive Hearing Impairment.” American Journal of Human Genetics 91 (4): 636–645.
Chicago author-date (all authors)
Schrauwen, Isabelle, Sarah Helfmann, Akira Inagaki, Friederike Predoehl, Mohammad Amin Tabatabaiefar, Maria Magdalena Picher, Manou Sommen, Celia Zazo Seco, Jaap Oostrik, Hannie Kremer, Annelies Dheedene, Charlotte Claes, Erik Fransen, Morteza Hashemzadeh Chaleshtori, Paul Coucke, Amy Lee, Tobias Moser, and Guy Van Camp. 2012. “A Mutation in CABP2, Expressed in Cochlear Hair Cells, Causes Autosomal-recessive Hearing Impairment.” American Journal of Human Genetics 91 (4): 636–645.
Vancouver
1.
Schrauwen I, Helfmann S, Inagaki A, Predoehl F, Tabatabaiefar MA, Picher MM, et al. A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment. AMERICAN JOURNAL OF HUMAN GENETICS. 2012;91(4):636–45.
IEEE
[1]
I. Schrauwen et al., “A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment,” AMERICAN JOURNAL OF HUMAN GENETICS, vol. 91, no. 4, pp. 636–645, 2012.
@article{4249711,
  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.}},
  author       = {{Schrauwen, Isabelle and Helfmann, Sarah and Inagaki, Akira and Predoehl, Friederike and Tabatabaiefar, Mohammad Amin and Picher, Maria Magdalena and Sommen, Manou and Seco, Celia Zazo and Oostrik, Jaap and Kremer, Hannie and Dheedene, Annelies and Claes, Charlotte and Fransen, Erik and Chaleshtori, Morteza Hashemzadeh and Coucke, Paul and Lee, Amy and Moser, Tobias and Van Camp, Guy}},
  issn         = {{0002-9297}},
  journal      = {{AMERICAN JOURNAL OF HUMAN GENETICS}},
  keywords     = {{CALMODULIN,GENE,NIGHT BLINDNESS,CONGENITAL DEAFNESS,CA2+ CHANNELS,CA(V)1.3 CHANNELS,CA2+-BINDING PROTEINS,CALCIUM-BINDING PROTEINS,IDENTIFICATION,INACTIVATION}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{636--645}},
  title        = {{A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment}},
  url          = {{http://dx.doi.org/10.1016/j.ajhg.2012.08.018}},
  volume       = {{91}},
  year         = {{2012}},
}

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