Abstract
Variants in CIB2 can underlie either Usher syndrome type I (USH1J) or nonsyndromic hearing impairment (NSHI) (DFNB48). Here, a novel homozygous missense variant c.196C>T and compound heterozygous variants, c.[97C>T];[196C>T], were found, respectively, in two unrelated families of Dutch origin. Besides, the previously reported c.272 T>C functional missense variant in CIB2 was identified in two families of Pakistani origin. The missense variants are demonstrated not to affect subcellular localization of CIB2 in vestibular hair cells in ex vivo expression experiments. Furthermore, these variants do not affect the ATP-induced calcium responses in COS-7 cells. However, based on the residues affected, the variants are suggested to alter αIIβ integrin binding. HI was nonsyndromic in all four families. However, deafness segregating with the c.272T>C variant in one Pakistani family is remarkably less severe than that in all other families with this mutation. Our results contribute to the insight in genotype–phenotype correlations of CIB2 mutations.
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Acknowledgements
We are thankful to the families for their participation in this study. We thank Saskia van der Velde-Visser for excellent technical assistance. This work was financially supported by grants from The Oticon Foundation (09-3742, to HK), ZonMW (40-00812-98-09047, to HK; 016.136.088, to MS; 016.136.091 to EvW and 40-42900-98-1006 to EvW). This study was partially sponsored by the National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) research grants (R01 DC012564 to ZMA and R01 DC011803 to SR). Part of this work was supported by a core grant from the COMSATS Institute of Information Technology.
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Seco, C., Giese, A., Shafique, S. et al. Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells. Eur J Hum Genet 24, 542–549 (2016). https://doi.org/10.1038/ejhg.2015.157
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DOI: https://doi.org/10.1038/ejhg.2015.157
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