Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene

Abstract

Hereditary non-syndromic profound deafness affects about 1 in 2000 children prior to language acquisition. In 80% of the cases, the mode of transmission is autosomal recessive. The number of genes involved in these recessive forms of isolated deafness (DFNB genes) has been estimated to between 30 and 100. So far, ten DFNB genes have been mapped to human chromosomes, one of which has been isolated2. By linkage analysis of a single family whose members were affected with profound deafness, some of them presenting with vestibular dysfunction, DFNB2 has been mapped to chromosome 11q13 (ref. 3). The gene responsible for a form of Usher syndrome type I, USH1B, has been assigned to the same chromosomal region4. Usher syndrome associates profound congenital deafness and vestibular dysfunction with retinitis pigmentosa. In the homologous murine region are located the shaker-1 mutations responsible for deafness and vestibular dysfunction. It has been demonstrated that the murine shaker-1 and human USH1B phenotypes result from mutations in the gene encoding myosin-VIIA5,6. Based on mapping data as well as on the similarities between the phenotypes of DFNB2-affected patients and shaker-1 mouse mutants, we have proposed that a defective myosin-VIIA may also be responsible for DFNB2 (ref. 1). Sequence analysis of each of the coding exons of the myosin-VIIA gene (MYO7A) was thus undertaken in the DFNB2-affected family. In the last nucleotide of exon 15, a G to A transition was detected, a type of mutation that is known to decrease the efficiency of splicing7‐14. Accordingly, this result shows that different mutations in MYO7A result in either an isolated or a syndromic form of deafness.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Petit, C. Genes responsible for human hereditary deafness: symphony of a thousand. Nature Genet. 14, 385–391 (1996).

    Article  CAS  Google Scholar 

  2. Kelsell, D.P. et al. Nature 387, 80–83 (1997).

    Article  CAS  Google Scholar 

  3. Guilford, P. et al. A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene. Hum. Mol. Genet. 3, 989–993 (1994).

    Article  CAS  Google Scholar 

  4. Smith, R.J.H. et al. Localization of two genes for Usher syndrome type I to chromosome 11. Genomics 14, 995–1002 (1992).

    Article  CAS  Google Scholar 

  5. Gibson, F. et al. A type VII myosin encoded by the mouse deafness gene Shaker-1. Nature 374, 62–64 (1995).

    Article  CAS  Google Scholar 

  6. Weil, D. et al. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature 374, 60–61 (1995).

    Article  CAS  Google Scholar 

  7. Vidaud, M.R. et al. A splice recognition G→C mutation in exon 1 of the human (3-globin gene inhibits pre-mRNA splicing: a mecanism for β+-thalassemia. Proc. Natl. Acad. Sci. USA. 86, 1041–1045 (1989).

    Article  CAS  Google Scholar 

  8. Weil, D. et al. Temperature-dependent expression of a collagen splicing defect in the fibroblasts of a patient with Ehlers-Danlos syndrome type VII. J. Biol. Chem. 264, 16804–16809 (1989).

    CAS  PubMed  Google Scholar 

  9. Weil, D., D'Alessio, M., Ramirez, F. & Eyre, D.R. Structural and functional characterization of a splicing mutation in the pro-alpha 2(l) collagen gene of an Ehlers-Danlos type VII patient . J Biol. Chem. 265, 16007–16011 (1990).

    CAS  PubMed  Google Scholar 

  10. Andrews, L.G. & Markert, M.L. Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency. J. Biol.Chem. 267, 7834–7838 (1992).

    CAS  PubMed  Google Scholar 

  11. Lind, B., van Solinge, W.W., Schwartz, M. & Thorsen, S. Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis. Blood 82, 2423–2432 (1993).

    CAS  PubMed  Google Scholar 

  12. Lemmink, H.H. et al. Mutations in the type IV collagen alpha 3 (COL4A3) gene in autosomal recessive Alport syndrome. Hum. Mol. Genet. 3, 1269–1273 (1994).

    Article  CAS  Google Scholar 

  13. Kuivaniemi, H., Tromp, G., Bergfeld, W.F., Kay, M. & Helm, T.N. Ehlers-Danlos syndrome type IV: a single base substitution of the last nucleotide of exon 34 in COL3A1 leads to exon skipping. J. Invest. Dermatol. 105, 352–356 (1995).

    Article  CAS  Google Scholar 

  14. Satokata, I., Uchiyama, M. & Tanaka, K. Two novel splicing mutations in the XPA gene in patients with group A xeroderma pigmentosum. Hum. Mol. Genet. 4, 1993–1994 (1995).

    Article  CAS  Google Scholar 

  15. Weil, D. et al. Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in the developing sensory organ. Proc. Natl. Acad Sci. USA 93, 3232–3237 (1996).

    Article  CAS  Google Scholar 

  16. Lévy, G. et al. Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB. Hum. Mol. Genet. 6, 111–116 (1997).

    Article  Google Scholar 

  17. Vale, R. Motor proteins, in Guidebook to the Cytoskeletal and Motor Proteins, (eds. KreisT, Vale R) 175–183 (Sambrook and Tooze, Oxford University Press, 1993).

    Google Scholar 

  18. Kyte, J. & Doolittle, R.F. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

  19. Rayment, I. et al. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science 261, 50–58 (1993).

    Article  CAS  Google Scholar 

  20. Engle, L.J. & Kennett, R.H. Cloning, analysis, and chromosomal localization of myoxin (MYH12), the human homologue to the mouse dilute gene. Genomics 19, 407–416 (1994).

    Article  CAS  Google Scholar 

  21. Cheney, R.E. et al. Brain myosin-V is a two-headed unconventional myosin with motor activity. Cell 75, 13–23 (1993).

    Article  CAS  Google Scholar 

  22. Vojtek, A.B., Hollenberg, S.M. & Cooper, J.A. Ras interacts directly with the serine/threonine kinase Raf. Cell 74, 205–214 (1993).

    Article  CAS  Google Scholar 

  23. Wayne, S. et al. Localization of the Usher syndrome type ID gene (UshID) to chromosome 10. Hum. Mol. Genet. 10, 1689–1692 (1996).

    Article  Google Scholar 

  24. Chaïb, H. et al. Mapping of DFNB12, a gene for a non-syndromal autosomal recessive deafness, to chromosome 10q21-22. Hum. Mol. Genet. 5, 1061–1064 (1996).

    Article  Google Scholar 

  25. Hasson, T., Heintzelman, M.B., Santos-Sacchi, J., Corey, D.P & Mooseker, M.S. Expression in cochlea and retina of myosin Vila, the gene product defective in Usher syndrome type 1 B. Proc. Natl. Acad. Sci. USA 92, 9815–9819 (1995).

    Article  CAS  Google Scholar 

  26. EI-Amraoui, A. et al. Human Usher IB/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells. Hum. Mol. Genet. 5, 1171–1178 (1996).

    Article  Google Scholar 

  27. Sahly, I., EI-Amraoui, A., Abitbol, M., Petit, C. & Dufier, J.-L Expression of myosin VIIA during mouse embryogenesis. Anat. Embryol. in press (1997).

  28. Tamagawa, Y. et al. A gene for a dominant form of non-syndromic sensorineural deafness (DFNA11) maps within the region containing the DFNB2 recessive deafness gene. Hum. Mol. Genet. 5, 849–852 (1996).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weil, D., Küssel, P., Blanchard, S. et al. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet 16, 191–193 (1997). https://doi.org/10.1038/ng0697-191

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0697-191

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing