TY - JOUR
T1 - A novel C-terminal CIB2 (calcium and integrin binding protein 2) mutation associated with non-syndromic hearing loss in a Hispanic family
AU - Patel, Kunjan
AU - Giese, Arnaud P.
AU - Grossheim, J. M.
AU - Hegde, Rashima S.
AU - Delio, Maria
AU - Samanich, Joy
AU - Riazuddin, Saima
AU - Frolenkov, Gregory I.
AU - Cai, Jinlu
AU - Ahmed, Zubair M.
AU - Morrow, Bernice E.
N1 - Publisher Copyright:
© 2015 Patel et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0133082
DO - 10.1371/journal.pone.0133082
M3 - Article
C2 - 26426422
AN - SCOPUS:84947221567
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e0133082
ER -