Abstract
Microdeletions Glu767(1-bp del), Thr967(1-bp del), and Leu1446(2-bp del) in the human USH2A gene have been reported to cause Usher syndrome type II, a disorder characterized by retinitis pigmentosa (RP) and mild-to-severe hearing loss. Each of these three frameshift mutations is predicted to lead to an unstable mRNA transcript that, if translated, would result in a truncated protein lacking the carboxy terminus. Here, we report Cys759Phe, a novel missense mutation in this gene that changes an amino-acid residue within the fifth laminin-epidermal growth factor-like domain of the USH2A gene and that is associated with recessive RP without hearing loss. This single mutation was found in 4.5% of 224 patients with recessive RP, suggesting that USH2A could cause more cases of nonsyndromic recessive RP than does any other gene identified to date.
Full Text
The Full Text of this article is available as a PDF (716.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boughman J. A., Vernon M., Shaver K. A. Usher syndrome: definition and estimate of prevalence from two high-risk populations. J Chronic Dis. 1983;36(8):595–603. doi: 10.1016/0021-9681(83)90147-9. [DOI] [PubMed] [Google Scholar]
- Cruickshanks K. J., Wiley T. L., Tweed T. S., Klein B. E., Klein R., Mares-Perlman J. A., Nondahl D. M. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The Epidemiology of Hearing Loss Study. Am J Epidemiol. 1998 Nov 1;148(9):879–886. doi: 10.1093/oxfordjournals.aje.a009713. [DOI] [PubMed] [Google Scholar]
- Eudy J. D., Weston M. D., Yao S., Hoover D. M., Rehm H. L., Ma-Edmonds M., Yan D., Ahmad I., Cheng J. J., Ayuso C. Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science. 1998 Jun 12;280(5370):1753–1757. doi: 10.1126/science.280.5370.1753. [DOI] [PubMed] [Google Scholar]
- Hagstrom S. A., North M. A., Nishina P. L., Berson E. L., Dryja T. P. Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa. Nat Genet. 1998 Feb;18(2):174–176. doi: 10.1038/ng0298-174. [DOI] [PubMed] [Google Scholar]
- Jain P. K., Lalwani A. K., Li X. C., Singleton T. L., Smith T. N., Chen A., Deshmukh D., Verma I. C., Smith R. J., Wilcox E. R. A gene for recessive nonsyndromic sensorineural deafness (DFNB18) maps to the chromosomal region 11p14-p15.1 containing the Usher syndrome type 1C gene. Genomics. 1998 Jun 1;50(2):290–292. doi: 10.1006/geno.1998.5320. [DOI] [PubMed] [Google Scholar]
- Liu X. Z., Hope C., Liang C. Y., Zou J. M., Xu L. R., Cole T., Mueller R. F., Bundey S., Nance W., Steel K. P. A mutation (2314delG) in the Usher syndrome type IIA gene: high prevalence and phenotypic variation. Am J Hum Genet. 1999 Apr;64(4):1221–1225. doi: 10.1086/302332. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu X. Z., Walsh J., Mburu P., Kendrick-Jones J., Cope M. J., Steel K. P., Brown S. D. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet. 1997 Jun;16(2):188–190. doi: 10.1038/ng0697-188. [DOI] [PubMed] [Google Scholar]
- Liu X. Z., Walsh J., Tamagawa Y., Kitamura K., Nishizawa M., Steel K. P., Brown S. D. Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene. Nat Genet. 1997 Nov;17(3):268–269. doi: 10.1038/ng1197-268. [DOI] [PubMed] [Google Scholar]
- Smith R. J., Berlin C. I., Hejtmancik J. F., Keats B. J., Kimberling W. J., Lewis R. A., Möller C. G., Pelias M. Z., Tranebjaerg L. Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet. 1994 Mar 1;50(1):32–38. doi: 10.1002/ajmg.1320500107. [DOI] [PubMed] [Google Scholar]
- Wagenaar M., van Aarem A., Huygen P., Pieke-Dahl S., Kimberling W., Cremers C. Hearing impairment related to age in Usher syndrome types 1B and 2A. Arch Otolaryngol Head Neck Surg. 1999 Apr;125(4):441–445. doi: 10.1001/archotol.125.4.441. [DOI] [PubMed] [Google Scholar]
- Weil D., Blanchard S., Kaplan J., Guilford P., Gibson F., Walsh J., Mburu P., Varela A., Levilliers J., Weston M. D. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature. 1995 Mar 2;374(6517):60–61. doi: 10.1038/374060a0. [DOI] [PubMed] [Google Scholar]
- Weil D., Küssel P., Blanchard S., Lévy G., Levi-Acobas F., Drira M., Ayadi H., Petit C. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet. 1997 Jun;16(2):191–193. doi: 10.1038/ng0697-191. [DOI] [PubMed] [Google Scholar]