![]() PDZD7 was proposed as a contributor of digenic inheritance with GPR98, and as a retinal disease modifier in USH2A patients. In addition to these 10 genes, three other genes have been associated with USH. Furthermore, most of these genes are also responsible for non-syndromic hearing loss or isolated RP. For USH3 only mutations in CLRN1 have been described, and a second locus was proposed, USH3B. Three genes have been found to cause USH2: USH2A (USH2A), GPR98 (USH2C) and DFNB31 (USH2D). For USH1 six genes have been identified: MYO7A (USH1B), USH1C (USH1C), CDH23 (USH1D), PCDH15 (USH1F), USH1G (USH1G) and CIB2 (USH1J) and two additional loci have been described: USH1E and USH1H. To date, 10 genes and three additional loci have been associated with the disease. However, in some patients the disease does not fit into any of these three subtypes, and they are classified as `atypical Usher syndrome'. Usher syndrome type III (USH3) is characterized by postlingual progressive hearing loss, RP with a variable age of onset and variable vestibular response ). Usher syndrome type II (USH2) patients display congenital moderate-severe hearing loss, onset of RP around or after puberty and normal vestibular function. Type I (USH1) is defined by profound congenital hearing loss, onset of RP usually within the first decade of life and an absence of vestibular function. According to the severity and progression of the disease, three clinical types are distinguished. USH has a remarkable clinical and genetic heterogeneity. Its prevalence ranges from 3 to 6.2 per 100,000 - and it is the most common form of hereditary syndromes combining hearing loss and retinitis pigmentosa. Usher syndrome (USH) is an autosomal recessive disease characterized by the association of sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. Targeted next generation sequencing allowed us to detect both point mutations and large rearrangements in a single experiment, minimizing the economic cost of the study, increasing the detection ratio of the genetic cause of the disease and improving the genetic diagnosis of Usher syndrome patients. These mutations included 21 missense, 8 nonsense, 9 frameshifts, 9 intronic mutations and 6 large rearrangements. Fifty-three different mutations were detected. We were able to detect biallelic mutations in one USH gene in 22 out of 32 USH patients (68.75%) and to identify 79.7% of the expected mutated alleles. ![]() Resultsįorty USH patients were successfully sequenced, 8 USH patients from the test group and 32 patients from the group composed of USH patients without genetic diagnosis. This cohort was divided into two groups: a test group of 11 patients with known mutations and another group of 33 patients with unknown mutations. A cohort of 44 patients suffering from Usher syndrome was selected for this study. MethodsĪ custom HaloPlex panel for Illumina platforms was designed to capture all exons of the 10 known causative Usher syndrome genes ( MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, GPR98, DFNB31 and CLRN1), the two Usher syndrome-related genes ( HARS and PDZD7) and the two candidate genes VEZT and MYO15A. Consequently, the aim of the present study was to develop a molecular diagnostics method for Usher syndrome, based on targeted next generation sequencing. To date, 10 genes have been associated with the disease, making its molecular diagnosis based on Sanger sequencing, expensive and time-consuming. ![]() It is clinically and genetically heterogeneous. Usher syndrome is an autosomal recessive disease that associates sensorineural hearing loss, retinitis pigmentosa and, in some cases, vestibular dysfunction. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |