A novel C-terminal CIB2 (calcium and integrin binding protein 2) mutation associated with non-syndromic hearing loss in a Hispanic family

Kunjan Patel, Arnaud P. Giese, J. M. Grossheim, Rashima S. Hegde, Maria Delio, Joy Samanich, Saima Riazuddin, Gregory I. Frolenkov, Jinlu Cai, Zubair M. Ahmed, Bernice E. Morrow

Research output: Contribution to journalArticle

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Abstract

Hearing loss is a complex disorder caused by both genetic and environmental factors. Previously, mutations in CIB2 have been identified as a common cause of genetic hearing loss in Pakistani and Turkish populations. Here we report a novel (c.556C>T; p.(Arg186Trp)) transition mutation in the CIB2 gene identified through whole exome sequencing (WES) in a Caribbean Hispanic family with non-syndromic hearing loss. CIB2 belongs to the family of calciumand integrin-binding (CIB) proteins. The carboxy-termini of CIB proteins are associated with calcium binding and intracellular signaling. The p.(Arg186Trp) mutation is localized within predicted type II PDZ binding ligand at the carboxy terminus. Our ex vivo studies revealed that the mutation did not alter the interactions of CIB2 with Whirlin, nor its targeting to the tips of hair cell stereocilia. However, we found that the mutation disrupts inhibition of ATP-induced Ca2+ responses by CIB2 in a heterologous expression system. Our findings support p. (Arg186Trp) mutation as a cause for hearing loss in this Hispanic family. In addition, it further highlights the necessity of the calcium binding property of CIB2 for normal hearing.

Original languageEnglish (US)
Article numbere0133082
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

integrins
Audition
hearing
Hearing Loss
Hispanic Americans
Integrins
binding proteins
Carrier Proteins
Calcium
mutation
calcium
Mutation
Stereocilia
Exome
endoplasmic reticulum glycoprotein p72
binding properties
Hearing
in vivo studies
hairs
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A novel C-terminal CIB2 (calcium and integrin binding protein 2) mutation associated with non-syndromic hearing loss in a Hispanic family. / Patel, Kunjan; Giese, Arnaud P.; Grossheim, J. M.; Hegde, Rashima S.; Delio, Maria; Samanich, Joy; Riazuddin, Saima; Frolenkov, Gregory I.; Cai, Jinlu; Ahmed, Zubair M.; Morrow, Bernice E.

In: PLoS One, Vol. 10, No. 10, e0133082, 01.10.2015.

Research output: Contribution to journalArticle

Patel, K, Giese, AP, Grossheim, JM, Hegde, RS, Delio, M, Samanich, J, Riazuddin, S, Frolenkov, GI, Cai, J, Ahmed, ZM & Morrow, BE 2015, 'A novel C-terminal CIB2 (calcium and integrin binding protein 2) mutation associated with non-syndromic hearing loss in a Hispanic family', PLoS One, vol. 10, no. 10, e0133082. https://doi.org/10.1371/journal.pone.0133082
Patel, Kunjan ; Giese, Arnaud P. ; Grossheim, J. M. ; Hegde, Rashima S. ; Delio, Maria ; Samanich, Joy ; Riazuddin, Saima ; Frolenkov, Gregory I. ; Cai, Jinlu ; Ahmed, Zubair M. ; Morrow, Bernice E. / A novel C-terminal CIB2 (calcium and integrin binding protein 2) mutation associated with non-syndromic hearing loss in a Hispanic family. In: PLoS One. 2015 ; Vol. 10, No. 10.
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