Analysis of the disease causing genes of primary ciliary dyskinesia by gene panel and whole exosome analysis
| Project/Area Number |
19K09886
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Mie University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北野 雅子 三重大学, 医学部附属病院, 助教 (20378334)
藤澤 隆夫 独立行政法人国立病院機構三重病院(臨床研究部), 独立行政法人国立病院機構三重病院, 名誉院長 (20511140)
中谷 中 三重大学, 医学部附属病院, 教授 (80237304)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 線毛 / 遺伝子 / ゲノム / パネル / エクソーム / 遺伝学的検査 / バリアント / 遺伝子変異 / 電子顕微鏡 / コピー数 / 咳嗽 |
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| Outline of Research at the Start |
臨床症状と経過から本症が疑われる患者について、次の３つの方法を用いて解析する。
①鼻腔一酸化窒素測定：鼻腔一酸化窒素濃度は本症の患者では低値を示すとされている。低値の患者については、次の、②、③を行う。
②電子顕微鏡検査による線毛の構造解析：鼻粘膜生検は、細胞診用のブラシを用いる。三重大学電顕室で標本作製と画像撮影を行う。
③遺伝子変異の解析：本症の原因遺伝子として知られている３２遺伝子について作成した遺伝子パネルにて、遺伝子変異の有無の検討を行ない、パネルで判明した変異についてはサンガー法による確認を行う。これらに変異がみられない場合、全エクソーム解析により解析する。
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| Outline of Final Research Achievements |
Primary ciliary dyskinesia is a hereditary disease that causes chronic nasal sinusitis, otitis media, bronchiectasis, and situs inversus due to pathogenic variants of cilia-related genes. About 50 causative genes are known, but the frequency of causative genes in Japan had been unknown. It is known that the causative gene differs depending on the race, and in order to clarify the causative gene in Japan efficiently, gene analysis by a panel consisting of 32 known genes, followed by whole exosome analysis in case the panel failed to reveal the causative genes, was performed. As a result, it was clarified that the deletion of both alleles of DRC1 was the most frequent gene variant, followed by DNAH5. DRC1 is rare in other races and is presumed to be the causative gene characteristic of Japan or East Asia.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦の原発性線毛運動不全症の原因遺伝子として、DRC1の両アレルの欠損とDNAH5の病的バリアントが多いことが判明した。これにより本邦における遺伝学的検査が推進されると考えられる。また、世界的にみてDRC1の広範囲な欠損は韓国人と日本人で報告されているのみであり、人種による差異があることは興味深い。
本症は小児慢性特定疾病であるが、成人においては指定難病ではない。患者は長期間にわたり呼吸機能障害に悩むので、今回の成果により指定難病申請を行い、指定難病となれば患者にとって得るところが大きい。
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Analysis of the clinical features of Japanese patients with primary ciliary dyskinesia.2022
Author(s)
Chiyonobu K, Xu Y, Feng G, Saso S, Ogawa S, Ikejiri M, Abo M, Kondo M, Gotoh S, Kubo H, Hosoki K, Nagao M, Fujisawa T, Nakatani K, Takeuchi K.
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Journal Title
Auris Nasus Larynx
Volume: 49
Issue: 2
Pages: 248-257
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Multicellular modeling of ciliopathy by combining iPS cells and microfluidic airway-on-a-chip technology.2021
Author(s)
Sone N, Konishi S, Igura K, Tamai K, Ikeo S, Korogi Y, Kanagaki S, Namba T, Yamamoto Y, Xu Y, Takeuchi K, Adachi Y, Chen-Yoshikawa TF, Date H, Hagiwara M, Tsukita S, Hirai T, Torisawa YS, Gotoh S.
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Journal Title
Sci Transl Med.
Volume: 7
Issue: 601
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Multifaceted analysis of Japanese cases of primary ciliary dyskinesia: Value of immunofluorescence for ciliary protein detection in patients with DNAH5 and DNAH11 mutations.2021
Author(s)
Kurokawa A, Kondo M, Orimo M, Honda N, Miyoshi A, Akaba T, Tsuji M, Nakatani K, Ikejiri M, Yagi O, Takeyama K, Takeuchi K, Tagaya E
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Journal Title
Respir Investig
Volume: 12
Issue: 4
Pages: 550-554
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population.2020
Author(s)
Takeuchi K, Xu Y, Kitano M, Chiyonobu K, Abo M, Ikegami K, Ogawa S, Ikejiri M, Kondo M, Gotoh S, Nagao M, Fujisawa T, Nakatani K.
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Journal Title
Mol Genet Genomic Med
Volume: 8(3)
Issue: 3
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] A pediatric case of productive cough caused by mutations in DNAH92020
Author(s)
Kazuhiko Takeuchi, Yifei Xu, Kazuki Chiyonobu, Hisami Kubo, Feng Guofei, Satoru Ogawa, Makoto Ikejiri, Kaname Nakatani , Satoko Usui, Sawako Masuda, Mizuho Nagao, Takao Fujisawa
Organizer
JSA/WAO Joint Congress 2020
Related Report
Int'l Joint Research
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