ORPHA: 231169, 886; DO: 0110836;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q25.1 | Usher syndrome, type IJ | 614869 | Autosomal recessive | 3 | CIB2 | 605564 |
A number sign (#) is used with this entry because of evidence that Usher syndrome type IJ (USH1J) is caused by homozygous mutation in the CIB2 gene (605564) on chromosome 15q24.
Mutation in the same gene causes autosomal recessive deafness-48 (DFNB48; 609439).
Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss.
For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900).
Ahmed et al. (2009) reported a large consanguineous Pakistani family (PKDF117) with Usher syndrome type I. Affected individuals had congenital profound sensorineural hearing loss, delayed onset of independent ambulation consistent with vestibular dysfunction, and variable severity of retinitis pigmentosa related to age.
The transmission pattern of Usher syndrome in the family reported by Ahmed et al. (2009) was consistent with autosomal recessive inheritance.
By genomewide linkage analysis of a consanguineous Pakistani family with autosomal recessive Usher syndrome, Ahmed et al. (2009) found linkage to an approximately 8-cM region on chromosome 15q between markers D15S988 and D15S1005.
In affected members of a large consanguineous Turkish family with Usher syndrome type IJ originally reported by Ahmed et al. (2009) as 'PKDF117,' Riazuddin et al. (2012) identified a homozygous mutation in the CIB2 gene (E64D; 605564.0004). Transfection of the mutation into COS-7 cells significantly decreased the ability of CIB2 to decrease ATP-induced calcium release from the cell compared to wildtype.
Ahmed, Z. M., Riazuddin, S., Khan, S. N., Friedman, P. L., Riazuddin, S., Friedman, T. B. USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23. Clin. Genet. 75: 86-91, 2009. [PubMed: 18505454] [Full Text: https://doi.org/10.1111/j.1399-0004.2008.01038.x]
Moller, C. G., Kimberling, W. J., Davenport, S. L. H., Priluck, I., White, V., Biscone-Halterman, K., Odkvist, L. M., Brookhouser, P. E., Lund, G., Grissom, T. J. Usher syndrome: an otoneurologic study. Laryngoscope 99: 73-79, 1989. [PubMed: 2909824] [Full Text: https://doi.org/10.1288/00005537-198901000-00014]
Riazuddin, S., Belyantseva, I. A., Giese, A. P. J., Lee, K., Indzhykulian, A. A., Nandamuri, S. P., Yousaf, R., Sinha, G. P., Lee, S., Terrell, D., Hegde, R. S., Ali, R. A., and 19 others. Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nature Genet. 44: 1265-1271, 2012. [PubMed: 23023331] [Full Text: https://doi.org/10.1038/ng.2426]