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2018 Fiscal Year Final Research Report

The identification of the novel gene mutation and development of the novel therapy for dyskeratosis congenita

Research Project

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Project/Area Number 16K09832
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNippon Medical School

Principal Investigator

Yamaguchi Hiroki  日本医科大学, 医学部, 准教授 (90297937)

Co-Investigator(Kenkyū-buntansha) 猪口 孝一  日本医科大学, 大学院医学研究科, 大学院教授 (10203267)
三宅 弘一  日本医科大学, 医学部, 准教授 (90267211)
Research Collaborator Terada Kazuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords先天性角化不全症 / テロメア制御遺伝子異常 / テロメラーゼ活性 / 新規遺伝子変異
Outline of Final Research Achievements

Telomerase activity in TERT carrying mutations detected in DKC patients (p.E280K or p.S334del) did not significantly differ from that in wild-type TERT. This makes it doubtful that the TERT mutations identified in DKC patients are causative for DKC. Next, we conducted a comprehensive analysis for DKC without the known gene mutation, and detected novel TEP1 mutations and ACD mutations. However, this ACD mutation did not cause binding inhibition of ACD and TINF2, and shelterin complexes destabilizes. The detected ACD mutation was not a responsibility in DKC.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

DKCは重症型と考えられるHoyeraal Hreidarsson syndrome (HHS) から軽症型の不全型DKCまでその病態や臨床像が多彩である。変異解析技術が発展したため遺伝子変異検索によって診断が明確となった症例も多くある。一方で遺伝子変異の結果をどのように判断すればよいのか判断が難しい症例もある。またDKCの約1/3の症例では責任遺伝子変異が同定されていないため遺伝子診断が出来ない場合もある。今回の研究成果で症例によっては遺伝子変異のみでDKCを診断するのは難しいことが明らかになった。

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Published: 2020-03-30  

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