title: Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Hamamatsu University School of Medicine, Hamamatsu, Japan. hosono@hama-med.ac.jp
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hosono
authors.forename: Chie
authors.initials: C
authors.lastname: Ishigami
authors.forename: Masayo
authors.initials: M
authors.lastname: Takahashi
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Park
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Akiko
authors.initials: A
authors.lastname: Hikoya
authors.forename: Taichi
authors.initials: T
authors.lastname: Fujita
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nishina
authors.forename: Jae Pil
authors.initials: JP
authors.lastname: Shin
authors.forename: In Taek
authors.initials: IT
authors.lastname: Kim
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Azuma
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
authors.forename: Miho
authors.initials: M
authors.lastname: Sato
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Shinsei
authors.initials: S
authors.lastname: Minoshima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hotta
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017434:Protein Structure, Tertiary; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology
chemical_list: C533105:EYS protein, human; D005136:Eye Proteins