title: Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48.
abstract: 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.
authors.affiliation: Division of Pediatric Otolaryngology/Head & Neck Surgery, Cincinnati Children's Hospital Medical Center, Ohio, USA.
authors.forename: Saima
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Inna A
authors.initials: IA
authors.lastname: Belyantseva
authors.forename: Arnaud P J
authors.initials: AP
authors.lastname: Giese
authors.forename: Kwanghyuk
authors.initials: K
authors.lastname: Lee
authors.forename: Artur A
authors.initials: AA
authors.lastname: Indzhykulian
authors.forename: Sri Pratima
authors.initials: SP
authors.lastname: Nandamuri
authors.forename: Rizwan
authors.initials: R
authors.lastname: Yousaf
authors.forename: Ghanshyam P
authors.initials: GP
authors.lastname: Sinha
authors.forename: Sue
authors.initials: S
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Terrell
authors.forename: Rashmi S
authors.initials: RS
authors.lastname: Hegde
authors.forename: Rana A
authors.initials: RA
authors.lastname: Ali
authors.forename: Saima
authors.initials: S
authors.lastname: Anwar
authors.forename: Paula B
authors.initials: PB
authors.lastname: Andrade-Elizondo
authors.forename: Asli
authors.initials: A
authors.lastname: Sirmaci
authors.forename: Leslie V
authors.initials: LV
authors.lastname: Parise
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Abdul
authors.initials: A
authors.lastname: Wali
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.forename: Shaheen N
authors.initials: SN
authors.lastname: Khan
authors.forename: Javed
authors.initials: J
authors.lastname: Akram
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Tiffany
authors.initials: T
authors.lastname: Cook
authors.forename: Elke K
authors.initials: EK
authors.lastname: Buschbeck
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Frolenkov
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Friedman
authors.forename: Zubair M
authors.initials: ZM
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D008040:Genetic Linkage; D018069:Hair Cells, Vestibular / Q000378:metabolism / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D052245:Usher Syndromes / Q000235:genetics* / Q000503:physiopathology; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development
chemical_list: D002135:Calcium-Binding Proteins; C532307:Cib2 protein, mouse