TY - JOUR
T1 - Genetic heterogeneity of usher syndrome
T2 - Analysis of 151 families with usher type I
AU - Astuto, Lisa M.
AU - Weston, Michael D.
AU - Carney, Carol A.
AU - Hoover, Denise M.
AU - Cremers, Cor W.R.J.
AU - Wagenaar, Mariette
AU - Moller, Claes
AU - Smith, Richard J.H.
AU - Pieke-Dahl, Sandra
AU - Greenberg, Jacquie
AU - Ramesar, Raj
AU - Jacobson, Samuel G.
AU - Ayuso, Carmen
AU - Heckenlively, John R.
AU - Tamayo, Marta
AU - Gorin, Michael B.
AU - Reardon, Willie
AU - Kimberling, William J.
N1 - Funding Information:
This work was supported in part by National Institute on Deafness and other Communicative Disorders (NIDCD) grants R01 DC00677-07 (to W.J.K.), P01 DC01813 (to W.J.K.), P60 DC00982 (to L.M.A.) and by a Foundation Fighting Blindness grant (to W.J.K.). The project was also supported by the Van Overbeek Foundation, De Drie Lichten, De Gelderse Blinden Verneniging (support to C.W.R.J.C. and M.W.), NIDCD grant R01 DC02842 (to R.J.H.S.), support by the Retinal Preservation Foundation of South Africa and a Foundation for Fighting Blindness in South Africa grant (to J.G.), National Eye Institute grant EY05627 (to S.G.J.), and by Research to Prevent Blindness and the Eye and Ear Foundation of Pittsburgh grants (to M.B.G.).
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.
AB - 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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U2 - 10.1086/316889
DO - 10.1086/316889
M3 - Article
C2 - 11060213
AN - SCOPUS:0033646476
SN - 0002-9297
VL - 67
SP - 1569
EP - 1574
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -