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)
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.
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Myosin-viia Gene; Integrin-binding Protein-1; I Usher-syndrome; Recessive Deafness; Hearing-loss; Biochemical-characterization; Retinitis-pigmentosa; Mutations; Locus; Maps
ISSN (print) / ISBN 1018-4813
Zeitschrift European Journal of Human Genetics
Quellenangaben Band: 24, Heft: 4, Seiten: 542-549
Verlag Nature Publishing Group
Institut(e) Institute of Human Genetics (IHG)