Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population
| Autor: | Hiroshi Nakanishi, Shuichi Yamamoto, Shinsei Minoshima, Hiroko Terasaki, Yang Zhao, Jae Pil Shin, Miho Sato, Yasuhiko Hirami, Akiko Hikoya, Mineo Kondo, Sachiko Nishina, Yoshihiro Hotta, Shinji Ueno, Tadashi Yokoi, Dong Ho Park, Noriyuki Azuma, In Taek Kim, Masayo Takahashi, Katsuhiro Hosono, Taichi Fujita, Chie Ishigami |
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| Rok vydání: | 2011 |
| Předmět: |
Male
DNA Mutational Analysis lcsh:Medicine medicine.disease_cause law.invention Exon Japan law Pathology lcsh:Science Polymerase chain reaction Genetics Mutation Multidisciplinary medicine.diagnostic_test Genomics Pedigree Medicine Female Retinitis Pigmentosa Research Article Clinical Pathology Sequence analysis Molecular Sequence Data Genes Recessive Biology Asian People Diagnostic Medicine Retinitis pigmentosa medicine Electroretinography Humans Family Amino Acid Sequence Allele Eye Proteins Gene Alleles Genetic testing Clinical Genetics Base Sequence lcsh:R medicine.disease eye diseases Protein Structure Tertiary Ophthalmology Genetics Population lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 2, p e31036 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation). Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X), were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan. |
| Databáze: | OpenAIRE |
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