primayr ciliary dyskinesia -Establishment of diagnostic methods and algorithms optimized for Japanese -

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: 公益財団法人結核予防会 結核研究所
• Principal Investigator: MORIMOTO KOZO 公益財団法人結核予防会 結核研究所, 抗酸菌部 細菌科, 研究員 (40511879)
• Co-Investigator(Kenkyū-buntansha): 慶長 直人 公益財団法人結核予防会 結核研究所, 副所長, 副所長 (80332386) ; 土方 美奈子 公益財団法人結核予防会 結核研究所, 生体防御部, 部長 (90332387)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 原発性線毛機能不全症候群 / 鼻腔NO測定 / 遺伝子検査 / 電子顕微鏡検査 / 副鼻腔気管支症候群 / 不妊症 / 非結核性抗酸菌症 / 気管支拡張症

Outline of Final Research Achievements

We aimed to establish the PCD diagnostic system following ATS guidelines and clarify the Japanese phenotypic and genotypic patterns. Seventy-six cases were screened and measured nasal NO concentrations. Of the 76 cases, 21 cases showed below the cutoff levels and were diagnosed as probable PCD cases. Gene analyses were performed in 49 cases, and 7 cases had compatible mutations. All 7 cases showed lower NO levels (7/21). We reevaluated a case diagnosed with diffuse panbronchiolitis refractory to macrolide therapy, and identified a large homozygous deletion spanning exons 1 to 4 of the DRC1. Further investigations in the U.S large cohort　found that this mutation might be a founder mutation in the Asian.　To improve awareness of the disease, we presented our data at several conferences and wrote a review article. Furthermore, we increased the number of genes related to PCD increased to more than 40 and improved the electron microscopy protocol, referring to the U.S method.

Free Research Field

内科系臨床医学 呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

ATSガイドラインに準じた手法を導入し、PCD診断体制を確立した。多くの症例が未診断であり、専門的管理を行う基盤の第一歩と考えている。多数例を集積し本邦実態を明らかとしていくことで難病指定に繋がることが期待される。