2023 Fiscal Year Final Research Report
Identification and characterization of novel mutations underlying autoinflammatory diseases showing pernio-like eruptions
| Project/Area Number |
19K08798
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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 53050:Dermatology-related
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| Research Institution | Hyogo Medical University (2020-2023)
Wakayama Medical University (2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
国本 佳代 和歌山県立医科大学, 医学部, 講師 (10438278)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Keywords | 凍瘡様皮疹 / 自己炎症性疾患 / 新規遺伝子変異 |
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| Outline of Final Research Achievements |
Since a heterozygous mutation in IFN regulatory genes, which have not been reported to be associated with any disease, was identified in a father and son who had recurrent fever and chilblain-like skin rash since infancy, functional analysis of the mutation was performed. The father- and son-derived samples showed abnormal IFN responses, but the same responses were not found in the gene-mutated cultured cells. Genetic analysis was performed on a case with generalized infiltrative erythema shortly after birth and cases with recurrent auricular chondritis and erythema multiforme-like skin rash in later life, and they were diagnosed as SAMD9L-associated autoinflammatory disease (SAAD) and VEXAS syndrome, respectively. In addition, genetic analyses have been performed on a young child with recurrent multiple panniculitis, an adult with progressive facial localized lipoatrophy, and an elderly male with severe pernio-like skin rash, and the pathogenicity of candidate genes is being examined.
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| Free Research Field |
皮膚炎症免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
乳児期から発熱と凍瘡様皮疹を反復する父子例に、これまでに疾患関連報告のないIFN調節遺伝子のヘテロ変異を同定し、その機能解析を本研究の中心課題として取り組んだが、疾患の原因と確定するには至らなかった。コロナ禍を挟み5年間研究を継続したにも関わらず、新規疾患関連遺伝子を見出すには至らなかったが、既報疾患ながら本邦初の症例を見出すなど、IRUDや厚労研究班などの大きな枠組みと連携し、臨床病理像と遺伝子変異の意義の双方をよく理解したphysician-scientistが臨床現場からターゲットを絞った研究を機能的に運営することで大きな枠組みの隙間を埋める、という当初の目標の一部は達成できたと考える。
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