Genetic heterogeneity of Usher syndrome: analysis of 151 families with Usher type I - PubMed (original) (raw)
. 2000 Dec;67(6):1569-74.
doi: 10.1086/316889. Epub 2000 Nov 1.
M D Weston, C A Carney, D M Hoover, C W Cremers, M Wagenaar, C Moller, R J 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
Affiliations
- PMID: 11060213
- PMCID: PMC1287932
- DOI: 10.1086/316889
Genetic heterogeneity of Usher syndrome: analysis of 151 families with Usher type I
L M Astuto et al. Am J Hum Genet. 2000 Dec.
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 chi(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.
Figures
Figure 1
Map of chromosome 10. The critical regions of USH1D and USH1F are outlined, and the markers used in the linkage analysis are listed, with their position (in cM) from the p-arm telomere.
Figure 2
Map of multipoint LOD scores for chromosome 10 markers and the families with _MYO7A_− Usher I: results of chromosome 10 multipoint analysis for all families, with the exclusion of the three 11q-linked and two French Acadian families. A LOD score of 1.03 lies between markers D10S1743 and D10S1665 between the two defined regions of USH1D and USH1F, and a LOD score of 2.89 lies within the USH1D region. Additional LOD scores, of 1.60 and 3.77, lie outside the regions of USH1F and USH1D, respectively.
Figure 3
Plot of chromosome 10 HOMOG analysis. Rolling χ2 values generated from the chromosome 10 multipoint analyses (data from fig. 2) are plotted against position (in cM). A maximum χ2 of 40.44 lies in USH1D and a second, lesser χ2 value of 28.71 lies just outside the USH1F region.
References
Electronic-Database Information
- GeneClinics, http://www.geneclinics.com
- Genome Database, The, http://www.gdb.org
- Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim (for MYO7A [MIM <276903>])
- Whitehead Institute for Biomedical Research/MIT Center for Genome Research, http://www.genome.wi.mit.edu
References
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