title: Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations.
abstract: The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD.
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Ophthalmology, Case Western Reserve University, Cleveland, OH 44124, USA ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44124, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maeda
authors.affiliation: Institute of Biomedical Research Innovation Hospital, Kobe 650-0047, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirami
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Ishigami
authors.affiliation: Department of Medical Ethics/Medical Genetics, Kyoto University School of Public Health, Kyoto 606-8501, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kosugi
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Mandai
authors.affiliation: Kobe City Medical Center General Hospital, Kobe 650-0047, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kurimoto
authors.affiliation: Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Takahashi