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Six years’ accomplishment of the Initiative on Rare and Undiagnosed Diseases: nationwide project in Japan to discover causes, mechanisms, and cures

2022; Springer Nature; Volume: 67; Issue: 9 Linguagem: Inglês

10.1038/s10038-022-01025-0

1435-232X

Yūji Takahashi, Hidetoshi Date, Hideki Oi, Takeya Adachi, Noriaki Imanishi, En Kimura, Hotake Takizawa, Shinji Kosugi, Naomichi Matsumoto, Kenjiro Kosaki, Yoichi Matsubara, Yukio Ando, Toshihisa Anzai, Tadashi Ariga, Yoshimitsu Fukushima, Yoshihiko Furusawa, Akira Ganaha, Yu‐ichi Goto, Kenichiro Hata, Masataka Honda, Kazumoto Iijima, Tsunakuni Ikka, Issei Imoto, Tadashi Kaname, Masao Kobayashi, Seiji Kojima, Hiroki Kurahashi, Shigeo Kure, Kenji Kurosawa, Yoshihiro Maegaki, Yoshio Makita, Tomohiro Morio, Ichiei Narita, Fumio Nomura, Tsutomu Ogata, Keiichi Ozono, Akira Oka, Nobuhiko Okamoto, Shinji Saitoh, Akihiro Sakurai, Fumio Takada, Tsutomu TAKAHASHI, Akira Tamaoka, Akihiro Umezawa, Akihiro Yachie, Kouichiro Yoshiura, Yasutsugu Chinen, Mariko Eguchi, Keishi Fujio, Kiminori Hosoda, Tomohiko Ichikawa, Toshitaka Kawarai, Tomoki Kosho, Mitsuo Masuno, Akie Nakamura, Takaya Nakane, Tomoo Ogi, Satoshi Okada, Yasushi Sakata, Toshiyuki Seto, Yoshiyuki Takahashi, Tadao Takano, Mitsuharu Ueda, Hideaki Yagasaki, Toshiyuki Yamamoto, Atsushi Watanabe, Yoshihiro Hotta, Akiharu Kubo, Hirofumi Maruyama, Keiji Moriyama, Eiji Nanba, Norio Sakai, Yoshiki Sekijima, Toru Shimosegawa, Tsutomu Takeuchi, Shin‐ichi Usami, Kazuhiko Yamamoto, Hidehiro Mizusawa,

Cancer Genomics and Diagnostics

The identification of causative genetic variants for hereditary diseases has revolutionized clinical medicine and an extensive collaborative framework with international cooperation has become a global trend to understand rare disorders. The Initiative on Rare and Undiagnosed Diseases (IRUD) was established in Japan to provide accurate diagnosis, discover causes, and ultimately provide cures for rare and undiagnosed diseases. The fundamental IRUD system consists of three pillars: IRUD diagnostic coordination, analysis centers (IRUD-ACs), and a data center (IRUD-DC). IRUD diagnostic coordination consists of clinical centers (IRUD-CLs) and clinical specialty subgroups (IRUD-CSSs). In addition, the IRUD coordinating center (IRUD-CC) manages the entire IRUD system and temporarily operates the IRUD resource center (IRUD-RC). By the end of March 2021, 6301 pedigrees consisting of 18,136 individuals were registered in the IRUD. The whole-exome sequencing method was completed in 5136 pedigrees, and a final diagnosis was established in 2247 pedigrees (43.8%). The total number of aberrated genes and pathogenic variants was 657 and 1718, among which 1113 (64.8%) were novel. In addition, 39 novel disease entities or phenotypes with 41 aberrated genes were identified. The 6-year endeavor of IRUD has been an overwhelming success, establishing an all-Japan comprehensive diagnostic and research system covering all geographic areas and clinical specialties/subspecialties. IRUD has accurately diagnosed diseases, identified novel aberrated genes or disease entities, discovered many candidate genes, and enriched phenotypic and pathogenic variant databases. Further promotion of the IRUD is essential for determining causes and developing cures for rare and undiagnosed diseases.