Mutations in the myosin VIIA gene cause non-syndromic recessive deafness

Abstract

Genetic hearing impairment affects around 1 in every 2,000 births1. The bulk (approximately 70%) of genetic deafness is non-syndromic, in which hearing impairment is not associated with any other abnormalities. Over 25 loci involved in non-syndromic deafness have been mapped and mutations in connexin 26 have been identified as a cause of non-sydromic deafness2. One locus for non-syndromic recessive deafness, DFNB2 (ref. 4), has been localized to the same chromosomal region, 11q14, as one of the loci, USH1B, underlying the recessive deaf-blind syndrome. Usher syndrome type 1b, which is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction and prepubertal onset of retinitis pigmentosa. Recently, it has been shown that a gene encoding an unconventional myosin, myosin VIIA, underlies the mouse recessive deafness mutation, shaker-1 (ref. 5) as well as Usher syndrome type 1b6. Mice with shaker-1 demonstrate typical neuroepithelial defects manifested by hearing loss and vestibular dysfunction but no retinal pathology. Differences in retinal patterns of expression may account for the variance in phenotype between shaker-1 mice and Usher type 1 syndrome7. Nevertheless, the expression of MYO7A in the neuroepithelium suggests that it should be considered a candidate for non-syndromic deafness in the human population. By screening families with non-syndromic deafness from China, we have identified two families carrying MYO7A mutations.

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References

  1. 1

    Fraser, G.R., Causes of Profound Deafness in Childhood. (Johns Hopkins University Press, Baltimore, 1976).

  2. 2

    Kelsell, D.P. et al. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387, 80–82.

  3. 3

    Steel, K.P. & Brown, S.D.M. Genetics of deafness. Curr. Opin. in Neurobiol. 6, 520–525 (1996).

  4. 4

    Guilford, P. et al. A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh1 gene. Hum. Mol. Genet. 3, 989–993 (1994).

  5. 5

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

  6. 6

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

  7. 7

    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).

  8. 8

    Liu, X.Z., Xu, L.R., Zhang, S.L. & Xu, Y. Epidemiological and genetic studies of congenital profound deafness. Am. J. Med. Genet. 53, 192–195 (1994).

  9. 9

    Anderson, H. & Wedenberg, E. Audiometric identification of normal hearingcarriers of genes for deafness. Act a. Otolaryngol. 65, 535–534 (1968).

  10. 10

    Meredith, R. et al. Audiometric detection of carriers of Usher's syndrome type II. J. Audiol. Med. 1, 11–19 (1992).

  11. 11

    Stephens, D. & Francis, M. The detection of carriers of genetic hearing loss. in: Genetics and Hearing Impairment (eds. Martini, A., Read, A. & Stephens, D. 100–108 (Whurr, London 1996).

  12. 12

    Weston, M.D. et al. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. Am. J. Hum. Genet. 59, 1074–1083 (1996).

  13. 13

    Cope, M.J.T.V., Whisstock, J., Rayment, I. & Kendrick-Jones, J. Conservation within the myosin motor domain: implications for structure and function. Structure 4, 969–987 (1996).

  14. 14

    Solc, C.K., Derfler, B.H., Duyk, G. & Corey, D.P. Molecular cloning of myosins from the bullfrog saccular macula: A candidate for the adaptation motor. Auditory Neurosci. 1, 63–75 (1994).

  15. 15

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

  16. 16

    Liu, X.Z., Newton, V.E., Steel, K.P. & Brown, S.D.M. Identification of a new mutation of the head region of myosin VII gene in Usher syndrome type 1. Hum. Mutat. (in press).

  17. 17

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

  18. 18

    Chen, Z.Y. et al. Molecular cloning and domain structure of human myosin Vila, the gene product defective in Usher syndrome 1 B. Genomics 36, 440–448 (1996).

  19. 19

    Liu, X.Z. & Xu, L.R. Non-syndromic genetic deafness: An analysis of audiograms. Ann. Otol. Rhinol. Laryngol. 103, 428–433 (1994).

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Liu, X., Walsh, J., Mburu, P. et al. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet 16, 188–190 (1997). https://doi.org/10.1038/ng0697-188

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