Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients (original) (raw)

. 1996 Nov;59(5):1074–1083.

Abstract

Usher syndrome type 1b (USH1B) is an autosomal recessive disorder characterized by congenital profound hearing loss, vestibular abnormalities, and retinitis pigmentosa. The disorder has recently been shown to be caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14. In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal coding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons. Twenty-three mutations were found segregating with the disease in 20 families. Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greatest percentage of observed mutant alleles (8/23, 31%). Six of the 13 mutations caused premature stop codons, 6 caused changes in the amino acid sequence of the myosin VIIa protein, and 1 resulted in a splicing defect. Three patients were homozygotes or compound heterozygotes for mutant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His-Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is presumed that the mutation on the other allele is present in the unscreened regions of the gene. None of the mutations reported here were observed in 96 unrelated control samples, although several polymorphisms were detected. These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16.

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Selected References

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  1. 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]
  2. 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]
  3. Guilford P., Ayadi H., Blanchard S., Chaib H., Le Paslier D., Weissenbach J., Drira M., Petit C. A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene. Hum Mol Genet. 1994 Jun;3(6):989–993. doi: 10.1093/hmg/3.6.989. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Keen J., Lester D., Inglehearn C., Curtis A., Bhattacharya S. Rapid detection of single base mismatches as heteroduplexes on Hydrolink gels. Trends Genet. 1991 Jan;7(1):5–5. doi: 10.1016/0168-9525(91)90004-a. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Kimberling W. J., Möller C. Clinical and molecular genetics of Usher syndrome. J Am Acad Audiol. 1995 Jan;6(1):63–72. [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. Mooseker M. S., Cheney R. E. Unconventional myosins. Annu Rev Cell Dev Biol. 1995;11:633–675. doi: 10.1146/annurev.cb.11.110195.003221. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Rayment I., Holden H. M., Whittaker M., Yohn C. B., Lorenz M., Holmes K. C., Milligan R. A. Structure of the actin-myosin complex and its implications for muscle contraction. Science. 1993 Jul 2;261(5117):58–65. doi: 10.1126/science.8316858. [DOI] [PubMed] [Google Scholar]
  13. Rayment I., Rypniewski W. R., Schmidt-Bäse K., Smith R., Tomchick D. R., Benning M. M., Winkelmann D. A., Wesenberg G., Holden H. M. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science. 1993 Jul 2;261(5117):50–58. doi: 10.1126/science.8316857. [DOI] [PubMed] [Google Scholar]
  14. Savov A., Angelicheva D., Balassopoulou A., Jordanova A., Noussia-Arvanitakis S., Kalaydjieva L. Double mutant alleles: are they rare? Hum Mol Genet. 1995 Jul;4(7):1169–1171. doi: 10.1093/hmg/4.7.1169. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Sébillon P., Beldjord C., Kaplan J. C., Brody E., Marie J. A T to G mutation in the polypyrimidine tract of the second intron of the human beta-globin gene reduces in vitro splicing efficiency: evidence for an increased hnRNP C interaction. Nucleic Acids Res. 1995 Sep 11;23(17):3419–3425. doi: 10.1093/nar/23.17.3419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Taylor E. W. Molecular muscle. Science. 1993 Jul 2;261(5117):35–36. doi: 10.1126/science.8316856. [DOI] [PubMed] [Google Scholar]
  18. Vikstrom K. L., Leinwand L. A. Contractile protein mutations and heart disease. Curr Opin Cell Biol. 1996 Feb;8(1):97–105. doi: 10.1016/s0955-0674(96)80053-6. [DOI] [PubMed] [Google Scholar]
  19. Watkins H., Seidman J. G., Seidman C. E. Familial hypertrophic cardiomyopathy: a genetic model of cardiac hypertrophy. Hum Mol Genet. 1995;4(Spec No):1721–1727. doi: 10.1093/hmg/4.suppl_1.1721. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]