医科学専攻

  • Master's Courses 
    修士課程
  • Doctoral Courses 
    博士課程

Pediatrics小児病態学

  • ゲノム解析
  • 小児血液腫瘍免疫疾患
  • 小児神経疾患
  • 先天代謝異常疾患
  • 小児内分泌疾患
  • 小児腎疾患
  • 先天性心疾患
  • 新生児疾患

STAFF

Professor

  • Kikuchi, AtsuoProfessor. 菊池 敦生 教授

Other Faculty / Staff

  • Sasahara, Yoji
    Assoc.Prof. 笹原 洋二 准教授
  • Uematsu, Mitsugu
    Assoc.Prof. 植松 貢准 教授

CONTACT

TEL:+81-22-717-7287
E-MAIL:atsuo.kikuchi.d4*tohoku.ac.jp
(「*」を「@」に変換してください)

OUTLINE

Identifying pathogenic variants in patients with undiagnosed genetic diseases is essential for understanding patient pathophysiology and providing better care. Until recently, the identification of novel causative genes for single-gene disorders (Mendelian disorders) required the analysis of large family trees. However, with the advent of comprehensive genetic analysis using next-generation sequencing, it has become possible to elucidate the molecular basis of single-gene diseases, even from a few isolated cases. In fact, through the molecular diagnosis of patients with undiagnosed diseases, we have established the concept of several novel rare genetic diseases (e.g., novel galactosemia, neurodevelopmental disorders, and cell membrane phospholipid metabolism disorders), some of which have not yet been reported elsewhere in the world and are unique. As the "relatively high frequency of rare genetic diseases" are resolved, the proportion of patients with undiagnosed genetic diseases that are "truly rare" seems to be increasing. However, the rarity of the disease makes it difficult to prove the relationship between the disease and the causative gene. We are attempting to propose new disease concepts for such cases by utilizing various disease-specific model organisms. Through our research, we aim to contribute to truly personalized medicine for each patient.

診断のつかない遺伝性疾患患者の病因遺伝子変異の同定は、患者の病態理解やより良いケアの提供に不可欠です。単一遺伝子病(メンデル遺伝病)の新規原因遺伝子同定のためにはこれまで大家系の解析が必要でしたが、近年の次世代シークエンサーによる網羅的遺伝学的解析手法の登場により、少数の孤発例からも単一遺伝子病の分子基盤を明らかにすることが可能となりました。実際、私達も未診断疾患患者の分子診断を通じていくつかの新規希少遺伝性疾患の概念(新規ガラクトース血症、神経発達疾患、細胞膜リン脂質代謝疾患など)を確立してきましたが、中には未だに世界にほかの報告がない、たった一例の疾患もありました。このように「比較的高頻度の希少遺伝性疾患」が解決するにつれ、診断のつかない遺伝性疾患患者として相対的に「真に希少な遺伝性疾患」の割合が高まっていると思われます。しかし希少であるがゆえに疾患と原因遺伝子の証明には困難が伴います。私達はこのような症例に対し、疾患に応じた様々なモデル生物の活用などにより、新規疾患概念の提唱を試みています。研究の結果、それぞれの患者さんに対する真の個別化医療に寄与できればと考えています。

ARTICLE

Segawa K, et al. A sublethal ATP11A mutation associated with neurological deterioration causes aberrant phosphatidylcholine flipping in plasma membranes. J Clin Invest. 131(18):e148005, 2021
URL:https://www.jci.org/articles/view/148005

Wada Y, et al. Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice. PLoS Genet. 16(2):e1008628, 2020
URL:https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008628

Iwasawa S, et al. Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. Ann Neurol. 85(6):927-933, 2019
URL:https://onlinelibrary.wiley.com/doi/10.1002/ana.25481

Wada Y, et al. Biallelic GALM pathogenic variants cause a novel type of galactosemia. Genet Med. 21(6):1286-1294, 2019
URL:https://www.gimjournal.org/article/S1098-3600(21)01653-1/fulltext

Takezawa Y, et al. Genomic analysis identifies masqueraders of full-term cerebral palsy. Ann Clin Transl Neurol. 5(5):538-551, 2018
URL:https://onlinelibrary.wiley.com/doi/10.1002/acn3.551

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