![]() The open arrow indicates a mutation in an intron and closed arrows indicate mutations in exons. All mutations were widely distributed almost throughout the entire USH2A region without any apparent hot spot. Upper, USH2A complementary DNA (cDNA) with exon boundaries. ( a) Schematic distribution of mutations identified in USH2A. 15, 16, 17 Usherin is a large protein comprising many functional domains ( Figure 1a). 11, 12, 13, 14 USH2A, which encodes usherin, accounts for 74â90% of USH2 cases. 6 Three causative genes have been identified: Usher syndrome 2A ( USH2A), G-protein coupled receptor 98 ( GPR98) and deafness, autosomal recessive 31 ( DFNB31). USH type 2 (USH2) is characterized by congenital mild-to-severe HL and a normal vestibular response it is the most common type and accounts for >50% of USH cases. 2, 3, 4, 5, 6, 7 The syndrome is clinically and genetically heterogeneous and can be classified into three clinical subtypes on the basis of the severity and progression of HL and the presence or absence of vestibular dysfunction. 1 It is the most common cause of combined deafness and blindness in industrialized countries, with a general prevalence of 3.5â6.2 per 100â000 live births. Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa (RP) and hearing loss (HL), with or without vestibular dysfunction. The fact that all patients carrying c.8559-2A>G came from western Japan suggests that the mutation is mainly distributed in that area indeed, most of the patients involved in this study came from eastern Japan, which contributed to the absence of c.8559-2A>G. Haplotype analysis of the c.8559-2G (mutated) alleles using 23 single nucleotide polymorphisms surrounding the mutation revealed an identical haplotype pattern of at least 635âkb in length, strongly suggesting that the mutation originated from a common ancestor. Meanwhile, we did not find the c.8559-2A>G in this study. This result indicates that the mutation spectrum for USH2A among Japanese patients largely differs from Caucasian, Jewish and Palestinian patients. We identified nine mutations, of which eight were novel. To obtain a more precise mutation spectrum, we analyzed further nine Japanese patients in this study. In a recent mutation screening of USH2A in Japanese USH2 patients, we identified 11 novel mutations in 10 patients and found the possible frequent mutation c.8559-2A>G in 4 of 10 patients. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A. Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss.
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