Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients

M. D. Western, P. M. Kelley, L. D. Overbeck, M. Wagenaar, D. J. Orten, T. Hasson, Z. Y. Chen, D. Corey, M. Mooseker, Janos Sumegi, C. Cremers, C. Möller, S. G. Jacobson, M. B. Gorin, W. J. Kimberling

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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 USHIB 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.

Original languageEnglish (US)
Pages (from-to)1074-1083
Number of pages10
JournalAmerican Journal of Human Genetics
Volume59
Issue number5
StatePublished - Oct 29 1996

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Usher Syndromes
Myosins
Mutation
Alleles
Heterozygote
Heteroduplex Analysis
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Retinitis Pigmentosa
Nonsense Codon
Homozygote
Hearing Loss
Genes
Amino Acid Sequence
Exons

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Western, M. D., Kelley, P. M., Overbeck, L. D., Wagenaar, M., Orten, D. J., Hasson, T., ... Kimberling, W. J. (1996). Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. American Journal of Human Genetics, 59(5), 1074-1083.

Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. / Western, M. D.; Kelley, P. M.; Overbeck, L. D.; Wagenaar, M.; Orten, D. J.; Hasson, T.; Chen, Z. Y.; Corey, D.; Mooseker, M.; Sumegi, Janos; Cremers, C.; Möller, C.; Jacobson, S. G.; Gorin, M. B.; Kimberling, W. J.

In: American Journal of Human Genetics, Vol. 59, No. 5, 29.10.1996, p. 1074-1083.

Research output: Contribution to journalArticle

Western, MD, Kelley, PM, Overbeck, LD, Wagenaar, M, Orten, DJ, Hasson, T, Chen, ZY, Corey, D, Mooseker, M, Sumegi, J, Cremers, C, Möller, C, Jacobson, SG, Gorin, MB & Kimberling, WJ 1996, 'Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients', American Journal of Human Genetics, vol. 59, no. 5, pp. 1074-1083.
Western MD, Kelley PM, Overbeck LD, Wagenaar M, Orten DJ, Hasson T et al. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. American Journal of Human Genetics. 1996 Oct 29;59(5):1074-1083.
Western, M. D. ; Kelley, P. M. ; Overbeck, L. D. ; Wagenaar, M. ; Orten, D. J. ; Hasson, T. ; Chen, Z. Y. ; Corey, D. ; Mooseker, M. ; Sumegi, Janos ; Cremers, C. ; Möller, C. ; Jacobson, S. G. ; Gorin, M. B. ; Kimberling, W. J. / Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. In: American Journal of Human Genetics. 1996 ; Vol. 59, No. 5. pp. 1074-1083.
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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 USHIB 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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AU - Orten, D. J.

AU - Hasson, T.

AU - Chen, Z. Y.

AU - Corey, D.

AU - Mooseker, M.

AU - Sumegi, Janos

AU - Cremers, C.

AU - Möller, C.

AU - Jacobson, S. G.

AU - Gorin, M. B.

AU - Kimberling, W. J.

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N2 - 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 USHIB 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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