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S. Jenkins, Z. Saihan, E. Haralambous, N. Waseem, S.S. Bhattacharya, A.T. Moore, M. Bitner–Glindzicz, A.R. Webster; Significance of the Usherin Cys759Phe Substitution in Non–Syndromic Retinal Dystrophy in the UK . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1804.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Association of retinitis pigmentosa and sensorineural hearing loss is the hallmark of Usher syndrome (USH). A missense variant (Cys759Phe) in the gene USH2A has been detected in over 4% of cases of autosomal recessive cases of RP (ARRP) without hearing loss, suggesting it to be the single most common nucleotide variant to cause RP in at least some populations. We report the findings of a survey of the same variant in a panel of autosomal recessive cases of RP without hearing loss and controls drawn from the United Kingdom. Methods: A panel of 289 unrelated probands with retinal dystrophy were recruited from patients presenting to Moorfields Eye Hospital. All persons had bilateral reduction of rod and cone Ganzfeld ERG amplitudes, ophthalmoscopic appearances consistent with RP and a family history consistent with AR inheritance (simplex or affected siblings). None had a history of hearing loss. 192 control DNAs were drawn from a random sample of unrelated blood donors from the UK. A further 84 control DNAs were derived from Caucasian volunteers working at the Institute of Ophthalmology or Moorfields with both parents born in the British Isles. Further, samples from 43 unrelated probands with Usher syndrome were also screened. A competitive PCR assay using fluorescently labelled primers was designed to determine the C759F genotype in a single reaction and the fluorescence detected using the ABI7700 analyzer. Comparisons of genotypes was performed using Fisher's Exact test. Results: Two out of the 552 control chromosomes were of the rare variant, both within heterozygotes. Five out of 578 chromosomes from those with ARRP were of the rare variant all within heterozygotes (Fisher Exact one–tailed p = 0.24). The rare variant was not detected in 86 Usher chromosomes. Of the 5 ARRP patients found to be heterozygous for C759F the phenotype was remarkably variable regarding fundoscopic appearance, age–of–onset and severity. Conclusions: Our results show the prevalence of the C759F change in ARRP patients drawn from the UK (1.7 percent) to be lower than in other populations. Additionally its prevalence seems not statistically greater than that of a control group. These findings suggest that the prevalence of this variant may be population–specific and that the haplotypic background of the change might influence its effect on retinal function.
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