Genetic heterogeneity of Usher syndrome type II in a Dutch population

S. Pieke-Dahl, A. Van Aarem, A. Dobin, C. W.R.J. Cremers, William J Kimberling

Research output: Contribution to journalArticle

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Abstract

The Usher syndromes are a group of autosomal recessive disorders characterised by retinitis pigmentosa (RP) with congenital, stable (non-progressive) sensorineural hearing loss. Profound deafness, RP, and no vestibular responses are features of Usher type I, whereas moderate to severe hearing loss and RP with normal vestibular function describe Usher type II. The gene responsible for most cases of Usher II, USH2a, is on chromosome 1q41; at least one other Usher II gene (as yet unlinked) is known to exist. Usher III presents with a progressive hearing loss that can mimic the audiometric profile seen in Usher II. A gene causing Usher III in a group of Finnish families, USH3, resides on chromosome 3q. Since the phenotypes for Usher II and III overlap, it is important to determine how frequently Usher IIa, Usher IIb, and Usher III occur in a clinical population of non-Usher I patients. DNA was collected from 29 Dutch families and genotyped with six DNA markers known to flank the USH2a gene closely, and with five markers that flank USH3. Results of haplotype and linkage analysis were consistent with linkage to the USH2a locus in 26 of these 29 Dutch families. Three families displayed no linkage to 1q41 markers, and one of these three families appeared unlinked to 3q markers as well; current haplotypes of the other two families are inconclusive for linkage with the USH3 locus without further genotyping. While an A test for heterogeneity of USH2a was statistically significant, no convincing evidence of linkage to USH3 was found in this Dutch sample. Consequently, the frequency of the unlinked variety of Usher IIa (Usher IIb) in The Netherlands was estimated as 0.104. To determine if marker alleles could be used to differentiate Usher type IIa from Usher IIb, parental chromosomes of the 26 Usher IIa families were analysed for significant non-random association of specific alleles from flanking loci with USH2a, but no linkage disequilibrium was observed in this Dutch population.

Original languageEnglish (US)
Pages (from-to)753-757
Number of pages5
JournalJournal of medical genetics
Volume33
Issue number9
StatePublished - Sep 25 1996

Fingerprint

Usher Syndromes
Genetic Heterogeneity
Retinitis Pigmentosa
Population
Chromosomes
Hearing Loss
Haplotypes
Genes
Alleles
Sensorineural Hearing Loss
Linkage Disequilibrium
Deafness
Genetic Markers
Netherlands
Phenotype
DNA

Keywords

  • Dutch population
  • Genetic heterogeneity
  • Usher syndrome type II

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Pieke-Dahl, S., Van Aarem, A., Dobin, A., Cremers, C. W. R. J., & Kimberling, W. J. (1996). Genetic heterogeneity of Usher syndrome type II in a Dutch population. Journal of medical genetics, 33(9), 753-757.

Genetic heterogeneity of Usher syndrome type II in a Dutch population. / Pieke-Dahl, S.; Van Aarem, A.; Dobin, A.; Cremers, C. W.R.J.; Kimberling, William J.

In: Journal of medical genetics, Vol. 33, No. 9, 25.09.1996, p. 753-757.

Research output: Contribution to journalArticle

Pieke-Dahl, S, Van Aarem, A, Dobin, A, Cremers, CWRJ & Kimberling, WJ 1996, 'Genetic heterogeneity of Usher syndrome type II in a Dutch population', Journal of medical genetics, vol. 33, no. 9, pp. 753-757.
Pieke-Dahl S, Van Aarem A, Dobin A, Cremers CWRJ, Kimberling WJ. Genetic heterogeneity of Usher syndrome type II in a Dutch population. Journal of medical genetics. 1996 Sep 25;33(9):753-757.
Pieke-Dahl, S. ; Van Aarem, A. ; Dobin, A. ; Cremers, C. W.R.J. ; Kimberling, William J. / Genetic heterogeneity of Usher syndrome type II in a Dutch population. In: Journal of medical genetics. 1996 ; Vol. 33, No. 9. pp. 753-757.
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