研究テーマ一覧>テーマ8 前へ 次へ

テーマ8:遺伝性白質脳症の臨床病理学的・分子遺伝学的研究

神経腫大軸索を伴う遺伝性びまん性白質脳症(Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids: HDLS)は、成人期に認知機能低下、精神症状、運動障害や痙攣発作を呈する常染色体優性遺伝性の若年性認知症で、画像的には大脳白質病変を伴う。神経病理学的には大脳白質の広範な軸索脱落と腫大軸索(スフェロイド)がみられる。2011年12月に本疾患の原因遺伝子がCSF1R (colony stimulating factor - 1 receptor)と報告され、当科では本邦初の変異同定例 (家族性) やde novo症例を報告してきた。また全国施設より依頼を受けCSF1R検査を行い、変異陽性例および陰性例の臨床・脳画像所見を解析してHDLSの特徴を明らかにしてきた。培養細胞にCSF1R変異を発現させ、変異がもたらすCSF1Rシグナル異常を明らかにする試みも行っている。

前頭頭頂葉優位の脳萎縮、半卵円から側脳室周囲の白質病変、脳梁の萎縮と異常信号
前頭頭頂葉優位の脳萎縮、半卵円から側脳室周囲の白質病変、脳梁の萎縮と異常信号
軸索脱落と腫大軸索(スフェロイド)
軸索脱落と腫大軸索(スフェロイド)

関連した主な業績・発表

  • Kinoshita M, Yoshida K, Oyanagi K, et al. Hereditary diffuse leukoencephalopathy with axonal spheroids caused by R782H mutation in CSF1R: Case report. J Neurol Sci 318 (1-2): 115-118, 2012.
  • Kondo Y, Kinoshita M, Fukushima K, et al. Early involvement of the corpus callosum in a patient with hereditary diffuse leukoencephalopathy with spheroids carrying the de novo K793T mutation of CSF1R. Intern Med 52 (4): 503-506, 2013.
  • Saitoh B, Yamasaki R, Hayashi S, et al. A case of hereditary diffuse leukoencephalopathy with axonal spheroids caused by a de novo mutation in CSF1R masquerading as primary progressive multiple sclerosis. Mult Scler 19 (10): 1367-1370, 2013.
  • Kimura T, Ishizawa K, Mitsufuji T, et al. A clinicopathological and genetic study of sporadic diffuse leukoencephalopathy with spheroids: A report of two cases. Neuropathol Appl Neurobiol 39: 837-843, 2013.
  • Saitoh B, Yoshida K, Hayashi S, et al. Sporadic hereditary diffuse leukoencephalopathy with axonal spheroids showing numerous lesions with restricted diffusivity caused by a novel splice site mutation in the CSF1R gene. Clin Exp Neuroimmunol 4: 76-81, 2013.
  • Kinoshita M, Kondo Y, Yoshida K, et al. Corpus callosum atrophy in hereditary diffuse leukoencephalopathy with neuroaxonal spheroids: an MRI-based study. Intern Med 53 (1): 21-27, 2014.
  • Sasaki A, Kakita A, Yoshida K, et al. Variable expression of microglial DAP12 and TREM2 genes in Nasu-Hakola disease. Neurogenetics 16(4):265-76, 2015.
  • Jin C, Washimi Y, Yoshida K, et al. Characterization of spheroids in hereditary diffuse leukoencephalopathy with axonal spheroids. J Neurol Sci 352(1-2): 74-78, 2015.
  • Lee D, Yun JY, Jeong JH, et al. Clinical evolution, neuroimaging, and volumetric analysis of a patient with a CSF1R mutation who presented with progressive nonfluent aphasia. Parkinsonism Relat Disord 21: 817-820, 2015.
  • Kondo Y, Kinoshita M, Yoshida T, et al. Unexpected occurrence of fetal hemophagocytic syndrome in a patient with hereditary diffuse leukoencephalopathy with spheroids. Case Rep Clin Med 5: 77-84, 2016.