Genetic heterogeneity of usher syndrome

Analysis of 151 families with usher type I

L. M. Astuto, Michael Weston, C. A. Carney, D. M. Hoover, C. W R J Cremers, M. Wagenaar, C. Moller, R. J H Smith, S. Pieke-Dahl, J. Greenberg, R. Ramesar, S. G. Jacobson, C. Ayuso, J. R. Heckenlively, M. Tamayo, M. B. Gorin, W. Reardon, W. J. Kimberling

Research output: Contribution to journalArticle

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Abstract

Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher L of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USHIF, on chromosome 10. A HOMOG χ(2/(1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.

Original languageEnglish
Pages (from-to)1569-1574
Number of pages6
JournalAmerican Journal of Human Genetics
Volume67
Issue number6
DOIs
StatePublished - 2000

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Usher Syndromes
Genetic Heterogeneity
Chromosomes, Human, Pair 10
Mutation
Genes
Retinitis Pigmentosa
Hearing Loss

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Astuto, L. M., Weston, M., Carney, C. A., Hoover, D. M., Cremers, C. W. R. J., Wagenaar, M., ... Kimberling, W. J. (2000). Genetic heterogeneity of usher syndrome: Analysis of 151 families with usher type I. American Journal of Human Genetics, 67(6), 1569-1574. https://doi.org/10.1086/316889

Genetic heterogeneity of usher syndrome : Analysis of 151 families with usher type I. / Astuto, L. M.; Weston, Michael; Carney, C. A.; Hoover, D. M.; Cremers, C. W R J; Wagenaar, M.; Moller, C.; Smith, R. J H; Pieke-Dahl, S.; Greenberg, J.; Ramesar, R.; Jacobson, S. G.; Ayuso, C.; Heckenlively, J. R.; Tamayo, M.; Gorin, M. B.; Reardon, W.; Kimberling, W. J.

In: American Journal of Human Genetics, Vol. 67, No. 6, 2000, p. 1569-1574.

Research output: Contribution to journalArticle

Astuto, LM, Weston, M, Carney, CA, Hoover, DM, Cremers, CWRJ, Wagenaar, M, Moller, C, Smith, RJH, Pieke-Dahl, S, Greenberg, J, Ramesar, R, Jacobson, SG, Ayuso, C, Heckenlively, JR, Tamayo, M, Gorin, MB, Reardon, W & Kimberling, WJ 2000, 'Genetic heterogeneity of usher syndrome: Analysis of 151 families with usher type I', American Journal of Human Genetics, vol. 67, no. 6, pp. 1569-1574. https://doi.org/10.1086/316889
Astuto, L. M. ; Weston, Michael ; Carney, C. A. ; Hoover, D. M. ; Cremers, C. W R J ; Wagenaar, M. ; Moller, C. ; Smith, R. J H ; Pieke-Dahl, S. ; Greenberg, J. ; Ramesar, R. ; Jacobson, S. G. ; Ayuso, C. ; Heckenlively, J. R. ; Tamayo, M. ; Gorin, M. B. ; Reardon, W. ; Kimberling, W. J. / Genetic heterogeneity of usher syndrome : Analysis of 151 families with usher type I. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 6. pp. 1569-1574.
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T2 - Analysis of 151 families with usher type I

AU - Astuto, L. M.

AU - Weston, Michael

AU - Carney, C. A.

AU - Hoover, D. M.

AU - Cremers, C. W R J

AU - Wagenaar, M.

AU - Moller, C.

AU - Smith, R. J H

AU - Pieke-Dahl, S.

AU - Greenberg, J.

AU - Ramesar, R.

AU - Jacobson, S. G.

AU - Ayuso, C.

AU - Heckenlively, J. R.

AU - Tamayo, M.

AU - Gorin, M. B.

AU - Reardon, W.

AU - Kimberling, W. J.

PY - 2000

Y1 - 2000

N2 - Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher L of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USHIF, on chromosome 10. A HOMOG χ(2/(1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.

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