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Progressive myoclonus epilepsy: extraneuronal brown pigment deposition and system neurodegeneration in the brains of J apanese patients with novel SCARB2 mutations
Author(s) -
Fu YongJuan,
Aida Izumi,
Tada Masayoshi,
Tada Mari,
Toyoshima Yasuko,
Takeda Shigeki,
Nakajima Takashi,
Naito Haruhiko,
Nishizawa Masatoyo,
Onodera Osamu,
Kakita Akiyoshi,
Takahashi Hitoshi
Publication year - 2014
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12057
Subject(s) - frameshift mutation , myoclonus , progressive myoclonus epilepsy , gliosis , neurodegeneration , pathology , epilepsy , medicine , gene mutation , ataxia , neuropathology , nonsense mutation , endocrinology , biology , mutation , disease , neuroscience , genetics , gene , missense mutation
Aims Mutations in the SCARB2 gene cause a rare autosomal recessive disease, progressive myoclonus epilepsy ( PME ) with or without renal failure, the former also being designated action myoclonus‐renal failure syndrome. Although reported cases have been accumulating, only a few have described its neuropathology. We studied two J apanese patients with PME without renal failure, in whom the ages at onset and disease durations were 45 and 20 years, and 14 and 8.5 years respectively. Methods Sequencing and restriction analysis of the SCARB2 gene and neuropathological examination with immunohistochemistry were performed. Results Gene analyses revealed novel homozygous frameshift and nonsense mutations in the SCARB2 gene. Both cases exhibited deposition of brown pigment in the brain, especially the cerebellar and cerebral cortices. Ultrastructurally, the pigment granules were localized in astrocytes. Neuronal loss and gliosis were also evident in the brain, including the pallidoluysian and cerebello‐olivary systems. The spinal cord was also affected. Such changes were less severe in one patient with late‐onset disease than in the other patient with early‐onset disease. In brain and kidney sections, immunostaining with an antibody against the C ‐terminus of human SCARB 2 revealed decreased levels and no expression of the protein respectively. Conclusions The frameshift mutation detected in the patient with late‐onset disease is a hitherto undescribed, unique type of SCARB2 gene mutation. The present two patients are the first reported to have clearly demonstrated both extraneuronal brown pigment deposition and system neurodegeneration as neuropathological features of PME with SCARB2 mutations.

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