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JL Grimsby, EL Berson, TP Dryja; Mutation Screening of the USH3A Gene in Patients with Retinitis Pigmentosa with Partial Hearing Loss . Invest. Ophthalmol. Vis. Sci. 2002;43(13):796.
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Purpose: Three mutations in the USH3A gene (chromosome 3q21-25) have recently been reported in patients from Finland and Italy with Usher syndrome type III, a disease characterized by post-lingual progressive hearing loss, retinal degeneration, and, in some cases, vestibular dysfunction (Sankila et al., Am J Hum Genet 69:673, 2001). The purpose of this study was to determine the prevalence of USH3A mutations among North American patients with retinitis pigmentosa and partial hearing loss irrespective of age of onset of hearing loss. Since it has been proposed that there may be a digenic interaction between USH3A and MYO7A (Adato et al., Am J Hum Genet 65:261,1999), we also analyzed several patients with Usher syndrome type I who were found to be heterozygotes with a mutant MYO7A allele. Methods: Oligonucleotide primers based on the flanking intron sequences were designed and used to amplify each of the 4 USH3A exons in 72 patients (those patients with known USH2A mutations were excluded). Age of onset of hearing loss varied among the 72 patients: 26 reported onset at birth or early childhood (≤5 years of age), 5 during childhood (between ages 5 and 18), 3 during adulthood (≥18 years), and 38 reported hearing loss but the age of onset was not precisely specified. Amplified exons were examined using the single-strand conformation polymorphism technique (SSCP) to find sequence variants. All variants were sequenced. Some patients were screened using direct sequencing only. In addition, we screened 9 patients with Usher syndrome type I who had one identified mutant MYO7A allele from an earlier study. Results: One patient was heterozygous for an intron change (IVS3-9,G≷A) and another was heterozygous for a change in the 3' untranslated region (G≷A, 45 bp downstream of the stop codon). Both changes were interpreted as nonpathogenic USH3A alleles. No definite pathogenic mutations were found. Conclusion: The USH3A gene does not appear to be the cause of Usher syndrome among our group of North American patients, even among patients reporting the onset of hearing loss in childhood or adulthood.
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