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Genetic Heterogeneity of Usher Syndrome: Analysis of 151 Families with Usher Type I
Journal article   Open access   Peer reviewed

Genetic Heterogeneity of Usher Syndrome: Analysis of 151 Families with Usher Type I

Lisa M Astuto, Michael D Weston, Carol A Carney, Denise M Hoover, Cor W.R.J Cremers, Mariette Wagenaar, Claes Moller, Richard J.H Smith, Sandra Pieke-Dahl, Jacquie Greenberg, …
American journal of human genetics, Vol.67(6), pp.1569-1574
2000
DOI: 10.1086/316889
PMCID: PMC1287932
PMID: 11060213
url
https://doi.org/10.1086/316889View
Published (Version of record) Open Access

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 I. 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 USH1F, 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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