Haplotype analysis of the USH1D locus and genotype-phenotype correlations

Xue Z Liu, Susan H Blanton, M. Bitner-Glindzicz, A. Pandya, B. Landa, B. MacArdle, K. Rajput, S. Bellman, B. T. Webb, X. Ping, R. J H Smith, W. E. Nance

Research output: Contribution to journalArticle

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Abstract

Usher syndrome (USH) is characterised by hearing impairment and progressive pigmentary retinopathy. USH can be divided into three subtypes based on the severity and progression of the major clinical findings. These subtypes are genetically heterogeneous, with at least six loci for USH1, three for USH2 and one for USH3. In the present study, five unrelated consanguineous families with USH1 were analysed for linkage to markers flanking the six USH1 loci. Two of these families, one Pakistani and one Turkish, demonstrated linkage to the USH1D locus. In another family, haplotype segregation was consistent with linkage to USH1C. The remaining families were not linked to any of the six USH1 loci, providing support for the existence of at least one additional USH1 locus. Analysis of these two new USH1D families allowed us to narrow the USH1D candidate region to a 7.3-cM interval with a telomeric flanking marker at D10S1752. Comparison of the affected haplotypes in our Pakistani family with the original Pakistani USH1D family yielded no evidence for a founder effect. The identification of two additional affected families suggests that the USH1D may be a more common form of USH1 than originally suspected. The USH1D (CDH23) gene has recently been cloned. Mutation analysis has shown two different CDH23 mutations in the two Pakistani USH1D families studied, which confirmed our finding that there was no evidence for a founder effect by haplotype analysis. The interesting correlations between genotype and phenotype in CDH23 are also summarised.

Original languageEnglish
Pages (from-to)58-62
Number of pages5
JournalClinical Genetics
Volume60
Issue number1
DOIs
StatePublished - Aug 6 2001
Externally publishedYes

Fingerprint

Genetic Association Studies
Usher Syndromes
Haplotypes
Founder Effect
Mutation
Retinitis Pigmentosa
Hearing Loss
Genes

Keywords

  • CDH23
  • Haplotypye analysis
  • Retinitis pigmentosa
  • USH1D

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Haplotype analysis of the USH1D locus and genotype-phenotype correlations. / Liu, Xue Z; Blanton, Susan H; Bitner-Glindzicz, M.; Pandya, A.; Landa, B.; MacArdle, B.; Rajput, K.; Bellman, S.; Webb, B. T.; Ping, X.; Smith, R. J H; Nance, W. E.

In: Clinical Genetics, Vol. 60, No. 1, 06.08.2001, p. 58-62.

Research output: Contribution to journalArticle

Liu, XZ, Blanton, SH, Bitner-Glindzicz, M, Pandya, A, Landa, B, MacArdle, B, Rajput, K, Bellman, S, Webb, BT, Ping, X, Smith, RJH & Nance, WE 2001, 'Haplotype analysis of the USH1D locus and genotype-phenotype correlations', Clinical Genetics, vol. 60, no. 1, pp. 58-62. https://doi.org/10.1034/j.1399-0004.2001.600109.x
Liu, Xue Z ; Blanton, Susan H ; Bitner-Glindzicz, M. ; Pandya, A. ; Landa, B. ; MacArdle, B. ; Rajput, K. ; Bellman, S. ; Webb, B. T. ; Ping, X. ; Smith, R. J H ; Nance, W. E. / Haplotype analysis of the USH1D locus and genotype-phenotype correlations. In: Clinical Genetics. 2001 ; Vol. 60, No. 1. pp. 58-62.
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