Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1997 Oct;61(4):813–821. doi: 10.1086/514899

Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins.

A Adato 1, D Weil 1, H Kalinski 1, Y Pel-Or 1, H Ayadi 1, C Petit 1, M Korostishevsky 1, B Bonne-Tamir 1
PMCID: PMC1716000  PMID: 9382091

Abstract

Usher syndrome types I (USH1A-USH1E) are a group of autosomal recessive diseases characterized by profound congenital hearing loss, vestibular areflexia, and progressive visual loss due to retinitis pigmentosa. The human myosin VIIA gene, located on 11q14, has been shown to be responsible for Usher syndrome type 1B (USH1B). Haplotypes were constructed in 28 USH1 families by use of the following polymorphic markers spanning the USH1B locus: D11S787, D11S527, D11S1789, D11S906, D11S4186, and OMP. Affected individuals and members of their families from 12 different ethnic origins were screened for the presence of mutations in all 49 exons of the myosin VIIA gene. In 15 families myosin VIIA mutations were detected, verifying their classification as USH1B. All these mutations are novel, including three missense mutations, one premature stop codon, two splicing mutations, one frameshift, and one deletion of >2 kb comprising exons 47 and 48, a part of exon 49, and the introns between them. Three mutations were shared by more than one family, consistent with haplotype similarities. Altogether, 16 USH1B haplotypes were observed in the 15 families; most haplotypes were population specific. Several exonic and intronic polymorphisms were also detected. None of the 20 known USH1B mutations reported so far in other world populations were identified in our families.

Full text

PDF
813

Images in this article

816Figure 1
on p.816

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonné-Tamir B., Korostishevsky M., Kalinsky H., Seroussi E., Beker R., Weiss S., Godel V. Genetic mapping of the gene for Usher syndrome: linkage analysis in a large Samaritan kindred. Genomics. 1994 Mar 1;20(1):36–42. doi: 10.1006/geno.1994.1124. [DOI] [PubMed] [Google Scholar]
  2. Chaïb H., Kaplan J., Gerber S., Vincent C., Ayadi H., Slim R., Munnich A., Weissenbach J., Petit C. A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome 21q21. Hum Mol Genet. 1997 Jan;6(1):27–31. doi: 10.1093/hmg/6.1.27. [DOI] [PubMed] [Google Scholar]
  3. Chen Z. Y., Hasson T., Kelley P. M., Schwender B. J., Schwartz M. F., Ramakrishnan M., Kimberling W. J., Mooseker M. S., Corey D. P. Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B. Genomics. 1996 Sep 15;36(3):440–448. doi: 10.1006/geno.1996.0489. [DOI] [PubMed] [Google Scholar]
  4. Cheney R. E., Riley M. A., Mooseker M. S. Phylogenetic analysis of the myosin superfamily. Cell Motil Cytoskeleton. 1993;24(4):215–223. doi: 10.1002/cm.970240402. [DOI] [PubMed] [Google Scholar]
  5. Gibson F., Walsh J., Mburu P., Varela A., Brown K. A., Antonio M., Beisel K. W., Steel K. P., Brown S. D. A type VII myosin encoded by the mouse deafness gene shaker-1. Nature. 1995 Mar 2;374(6517):62–64. doi: 10.1038/374062a0. [DOI] [PubMed] [Google Scholar]
  6. Hasson T., Heintzelman M. B., Santos-Sacchi J., Corey D. P., Mooseker M. S. Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9815–9819. doi: 10.1073/pnas.92.21.9815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kaplan J., Gerber S., Bonneau D., Rozet J. M., Delrieu O., Briard M. L., Dollfus H., Ghazi I., Dufier J. L., Frézal J. A gene for Usher syndrome type I (USH1A) maps to chromosome 14q. Genomics. 1992 Dec;14(4):979–987. doi: 10.1016/s0888-7543(05)80120-x. [DOI] [PubMed] [Google Scholar]
  8. Kimberling W. J., Möller C. G., Davenport S., Priluck I. A., Beighton P. H., Greenberg J., Reardon W., Weston M. D., Kenyon J. B., Grunkemeyer J. A. Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11. Genomics. 1992 Dec;14(4):988–994. doi: 10.1016/s0888-7543(05)80121-1. [DOI] [PubMed] [Google Scholar]
  9. Krawczak M., Reiss J., Cooper D. N. The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet. 1992 Sep-Oct;90(1-2):41–54. doi: 10.1007/BF00210743. [DOI] [PubMed] [Google Scholar]
  10. Liu X. Z., Newton V. E., Steel K. P., Brown S. D. Identification of a new mutation of the myosin VII head region in Usher syndrome type 1. Hum Mutat. 1997;10(2):168–170. doi: 10.1002/(SICI)1098-1004(1997)10:2<168::AID-HUMU10>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  11. Lévy G., Levi-Acobas F., Blanchard S., Gerber S., Larget-Piet D., Chenal V., Liu X. Z., Newton V., Steel K. P., Brown S. D. Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB. Hum Mol Genet. 1997 Jan;6(1):111–116. doi: 10.1093/hmg/6.1.111. [DOI] [PubMed] [Google Scholar]
  12. Möller C. G., Kimberling W. J., Davenport S. L., Priluck I., White V., Biscone-Halterman K., Odkvist L. M., Brookhouser P. E., Lund G., Grissom T. J. Usher syndrome: an otoneurologic study. Laryngoscope. 1989 Jan;99(1):73–79. doi: 10.1288/00005537-198901000-00014. [DOI] [PubMed] [Google Scholar]
  13. Rayment I., Holden H. M., Sellers J. R., Fananapazir L., Epstein N. D. Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3864–3868. doi: 10.1073/pnas.92.9.3864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rees D. J., Ades S. E., Singer S. J., Hynes R. O. Sequence and domain structure of talin. Nature. 1990 Oct 18;347(6294):685–689. doi: 10.1038/347685a0. [DOI] [PubMed] [Google Scholar]
  15. Sheffield V. C., Beck J. S., Kwitek A. E., Sandstrom D. W., Stone E. M. The sensitivity of single-strand conformation polymorphism analysis for the detection of single base substitutions. Genomics. 1993 May;16(2):325–332. doi: 10.1006/geno.1993.1193. [DOI] [PubMed] [Google Scholar]
  16. Smith R. J., Lee E. C., Kimberling W. J., Daiger S. P., Pelias M. Z., Keats B. J., Jay M., Bird A., Reardon W., Guest M. Localization of two genes for Usher syndrome type I to chromosome 11. Genomics. 1992 Dec;14(4):995–1002. doi: 10.1016/s0888-7543(05)80122-3. [DOI] [PubMed] [Google Scholar]
  17. Smith R. J., Pelias M. Z., Daiger S. P., Keats B., Kimberling W., Hejtmancik J. F. Clinical variability and genetic heterogeneity within the Acadian Usher population. Am J Med Genet. 1992 Aug 1;43(6):964–969. doi: 10.1002/ajmg.1320430612. [DOI] [PubMed] [Google Scholar]
  18. Takeuchi K., Kawashima A., Nagafuchi A., Tsukita S. Structural diversity of band 4.1 superfamily members. J Cell Sci. 1994 Jul;107(Pt 7):1921–1928. doi: 10.1242/jcs.107.7.1921. [DOI] [PubMed] [Google Scholar]
  19. Titus M. A. Unconventional myosins: new frontiers in actin-based motors. Trends Cell Biol. 1997 Mar;7(3):119–123. doi: 10.1016/S0962-8924(97)01019-2. [DOI] [PubMed] [Google Scholar]
  20. Wayne S., Der Kaloustian V. M., Schloss M., Polomeno R., Scott D. A., Hejtmancik J. F., Sheffield V. C., Smith R. J. Localization of the Usher syndrome type ID gene (Ush1D) to chromosome 10. Hum Mol Genet. 1996 Oct;5(10):1689–1692. doi: 10.1093/hmg/5.10.1689. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Weil D., Levy G., Sahly I., Levi-Acobas F., Blanchard S., El-Amraoui A., Crozet F., Philippe H., Abitbol M., Petit C. Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3232–3237. doi: 10.1073/pnas.93.8.3232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Weston M. D., Kelley P. M., Overbeck L. D., Wagenaar M., Orten D. J., Hasson T., Chen Z. Y., Corey D., Mooseker M., Sumegi J. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. Am J Hum Genet. 1996 Nov;59(5):1074–1083. [PMC free article] [PubMed] [Google Scholar]
  24. Whitney M. A., Saito H., Jakobs P. M., Gibson R. A., Moses R. E., Grompe M. A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews. Nat Genet. 1993 Jun;4(2):202–205. doi: 10.1038/ng0693-202. [DOI] [PubMed] [Google Scholar]
  25. Wolenski J. S. Regulation of calmodulin-binding myosins. Trends Cell Biol. 1995 Aug;5(8):310–316. doi: 10.1016/s0962-8924(00)89053-4. [DOI] [PubMed] [Google Scholar]
  26. el-Amraoui A., Sahly I., Picaud S., Sahel J., Abitbol M., Petit C. Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. Hum Mol Genet. 1996 Aug;5(8):1171–1178. doi: 10.1093/hmg/5.8.1171. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES