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XZ Liu, XM Ouyang, JF Hejtmancik, SG Jacobson, AR Li, LL Du, VE Newton, WE Nance; Mutation analysis of USH genes in patients with USH and non-syndromic RP . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2391.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Usher syndrome (USH) is defined by the association of visual impairment due to RP and sensorineural deafness. The syndrome 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. So far, the causative genes have been identified for USH1B, USH1C, USH1D, USH1F, USH2A, and USH3. The aim of this study is to identify novel mutations, to determine the frequency and distribution of mutations, and to investigate the genotype-phenotype correlations at currently recognized genes for USH. Methods: We employed a sequential screening approach to analyze the role of cloned USH genes in a large collection of DNA from patients/families with USH and RP. 230 USH including 128 type 1, 78 type 2, and 24 type 3 (atypical) as well as 93 non-syndromic RP were included in the present study. Segregation analysis was carried out using the flanking markers around 10 USH loci in 42 suitable families. Detection of mutations will be staged by screening for common mutations in the first instance and progressively increasing the range of tests. Amplified fragments for exons of each gene were analysed by combined SSCP/heteroduplex method, and variant bands were sequenced. Results: We have identified a variety of mutations and polymorphisms in MYO7A, USH1C, and USH2A in USH patients and have shown no mutations in MYO7A and CDH23 in RP cases. The RP associated mutation (C759F) in USH2A was detected only in one RP patient. Screening for mutation in CDH23, PCDH15, and USH3 is underway. Conclusion: The recent identification of genes for UHS has opened an avenue to investigate molecular genetic basis of USH. We report the mutation screen results of the newly cloned USH genes. We have identified a number of novel mutations in our patient panels. Identification of novel mutations may provide insight into the phenotypic variation. Moreover, identification of patients/families that do not have mutations in the cloned USH genes would be essential for reducing the impact of heterogeneity on the search for new USH genes.
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