Kondo Hiroyuki
   Department   School of Medicine  Ophthalmology, Clinical Medical Sciences
Article types journal article
Language English
Peer review Peer reviewed
Title Molecular Diagnosis of 34 Japanese Families with Leber Congenital Amaurosis Using Targeted Next Generation Sequencing.
Journal Formal name:Scientific reports
Abbreviation:Sci Rep
ISSN code:20452322/20452322
Volume, Issue, Page 8(1),8279頁
Author and coauthor Hosono Katsuhiro, Nishina Sachiko, Yokoi Tadashi, Katagiri Satoshi, Saitsu Hirotomo, Kurata Kentaro, Miyamichi Daisuke, Hikoya Akiko, Mizobuchi Kei, Nakano Tadashi, Minoshima Shinsei, Fukami Maki, Kondo Hiroyuki, Sato Miho, Hayashi Takaaki, Azuma Noriyuki, Hotta Yoshihiro
Publication date 2018/05
Summary Leber congenital amaurosis (LCA) is a genetically and clinically heterogeneous disease, and represents the most severe form of inherited retinal dystrophy (IRD). The present study reports the mutation spectra and frequency of known LCA and IRD-associated genes in 34 Japanese families with LCA (including three families that were previously reported). A total of 74 LCA- and IRD-associated genes were analysed via targeted-next generation sequencing (TS), while recently discovered LCA-associated genes, as well as known variants not able to be screened using this approach, were evaluated via additional Sanger sequencing, long-range polymerase chain reaction, and/or copy number variation analyses. The results of these analyses revealed 30 potential pathogenic variants in 12 (nine LCA-associated and three other IRD-associated) genes among 19 of the 34 analysed families. The most frequently mutated genes were CRB1, NMNAT1, and RPGRIP1. The results also showed the mutation spectra and frequencies identified in the analysed Japanese population to be distinctly different from those previously identified for other ethnic backgrounds. Finally, the present study, which is the first to conduct a NGS-based molecular diagnosis of a large Japanese LCA cohort, achieved a detection rate of approximately 56%, indicating that TS is a valuable method for molecular diagnosis of LCA cases in the Japanese population.
DOI 10.1038/s41598-018-26524-z
PMID 29844330