ORPHA: 231169, 886; DO: 0110835;
Cytogenetic location: 15q22-q23 Genomic coordinates (GRCh38): 15:58,800,001-72,400,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 15q22-q23 | Usher syndrome, type 1H | 612632 | 2 |
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 consanguineous Pakistani family (PKDF125) with Usher syndrome type I. All affected individuals were reported to be deaf from birth, showed delayed motor development consistent with vestibular dysfunction, and showed variable severity of retinitis pigmentosa related to age.
By genomewide linkage analysis of 2 consanguineous Pakistani families with autosomal recessive Usher syndrome, Ahmed et al. (2009) identified a novel locus, which they termed USH1H, on chromosome 15q22-q23 (maximum 2-point lod score of 4.21 at marker ZA840/841 and 5.67 at marker D15S980, respectively). The shared 4.2-cM interval between markers D15S988 and D15S967 overlapped with DFNB48 (609439). The overlapping interval of USH1H and DFNB48 contains only the TLE3 gene (600190), and sequence analysis did not reveal any pathogenic alleles. Sequence analysis of genes in a 3.36-Mb candidate region, including ITGA11 (604789), CORO2B (605002), and KIF23 (605064), did not reveal any pathogenic mutations.
Exclusion Studies
In 1 of the Pakistani families with Usher syndrome (PKDF125) reported by Ahmed et al. (2009), Riazuddin et al. (2012) excluded mutations in the CIB2 gene (605564). The other family (PKDF117) was found to carry a homozygous mutation in the CIB2 gene (605564.0004); see USH1J (614869).
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]