Alterations of the CIB2 calcium-and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48

Saima Riazuddin, Inna A. Belyantseva, Arnaud P.J. Giese, Kwanghyuk Lee, Artur A. Indzhykulian, Sri Pratima Nandamuri, Rizwan Yousaf, Ghanshyam P. Sinha, Sue Lee, David Terrell, Rashmi S. Hegde, Rana A. Ali, Saima Anwar, Paula B. Andrade-Elizondo, Asli Sirmaci, Leslie V. Parise, Sulman Basit, Abdul Wali, Muhammad Ayub, Muhammad AnsarWasim Ahmad, Shaheen N. Khan, Javed Akram, Mustafa Tekin, Sheikh Riazuddin, Tiffany Cook, Elke K. Buschbeck, Gregory I. Frolenkov, Suzanne M. Leal, Thomas B. Friedman, Zubair M. Ahmed

Research output: Contribution to journalArticlepeer-review

187 Scopus citations


Sensorineural hearing loss is genetically heterogeneous. Here, we report that mutations in CIB2, which encodes a calcium-and integrin-binding protein, are associated with nonsyndromic deafness (DFNB48) and Usher syndrome type 1J (USH1J). One mutation in CIB2 is a prevalent cause of deafness DFNB48 in Pakistan; other CIB2 mutations contribute to deafness elsewhere in the world. In mice, CIB2 is localized to the mechanosensory stereocilia of inner ear hair cells and to retinal photoreceptor and pigmented epithelium cells. Consistent with molecular modeling predictions of calcium binding, CIB2 significantly decreased the ATP-induced calcium responses in heterologous cells, whereas mutations in deafness DFNB48 altered CIB2 effects on calcium responses. Furthermore, in zebrafish and Drosophila melanogaster, CIB2 is essential for the function and proper development of hair cells and retinal photoreceptor cells. We also show that CIB2 is a new member of the vertebrate Usher interactome.

Original languageEnglish
Pages (from-to)1265-1271
Number of pages7
JournalNature Genetics
Issue number11
StatePublished - Nov 2012

Bibliographical note

Funding Information:
We thank the families for their participation and cooperation. We also thank G.N. Sarangdhar, R. Rachel, T. Jaworek, V. Ponferrada and K. Gul for technical assistance and R.J. Morell, J. Schultz, D. Drayna, A. Swaroop and A.J. Griffith for critique of the manuscript. We thank T.M. Leisner (University of North Carolina at Chapel Hill) for the generous gift of antibodies to CIB. Genotyping services were provided to S.M.L. by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract (N01-HG-65403) from the US National Institutes of Health (NIH) to Johns Hopkins University. Z.M.A. is a recipient of a Research to Prevent Blindness Career Development Award. This work was also supported by funding from the Higher Education Commission and the Ministry of Science and Technology (Islamabad, Pakistan) to Sheikh Riazuddin and W.A., the International Center for Genetic Engineering and Biotechnology (Trieste, Italy) under project CRP/PAK08-01 contract 08/009 to Sheikh Riazuddin, the Cincinnati Children’s Hospital Research Foundation (CCHMC) Intramural Research Funds to Saima Riazuddin and Z.M.A., a National Science Foundation grant (IOS-1050754) to E.K.B., US National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) research grants R01 DC03594 and DC011651 to S.M.L., R01 HL092544 to L.V.P., R01 DC009645 to M.T., R01 DC008861 to G.I.F., R01 DC012564 and R00 DC009287 to Z.M.A., and R01 DC011803 and R01 DC011748 to Saima Riazuddin, and intramural funds from the NIDCD (DC000039-15) to T.B.F.

ASJC Scopus subject areas

  • Genetics


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