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Clinical and pathological studies of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R mutation in large Japanese families

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Abstract

We clarified the clinical and pathological aspects of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R heterozygous mutation in the Miyakonojo Basin, a region in southern Japan where the prevalence of ALS is 11.4 per 105 of the population. We studied 17 patients, including one autopsy case, in three FALS families with the mutation. The average age at disease onset in the families was 44.3±8.7 years, and the mean disease duration was 12±7.6 years, with a range of 6 to 30 years. Ten of 17 patients were unable to walk by the mean age of 56.4±12.2 years. The initial symptom was muscle weakness in the distal leg muscle in all patients. The autopsy findings of one FALS patient showed atrophy of lateral and anterior funiculi, decreased numbers of anterior horn cells, preserved posterior funiculus and absence of neuronal inclusion bodies. Percentages of mutant SOD1 protein measured by mass spectrometry were 14% in erythrocytes, 43% in the spinal cord, 47% in the iliopsoas muscle and 60% in the diaphragm. In this study, we confirmed that FALS with SOD1 H46R mutation showed uniform initial symptoms and slow disease progression with intra-familial variation of disease severity and that inclusion body formation is not essential in FALS with this mutation.

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Acknowledgements

We express our appreciation to Dr. Jyoji Wakimoto (National Minamikyusyu Hospital, Kagoshima, Japan) for conducting the autopsy. We are grateful to Dr. Arlene R. Ng of Kagoshima University Faculty of Medicine for critical review. We also thank Ms. Yoko Tomita for her excellent technical assistance. This work was supported in part by a Research Grant (10B-4) for Nervous and Mental Disorders and a Research Grant (6-2A) for Central Nervous System Degenerative Disorders from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Kagoshima University Faculty of Medicine, Kagoshima, Japan

    Takayo Arisato, Mitsuhiro Osame & Masanori Nakagawa

  2. Division of Molecular Pathology and Genetic Epidemiology, Kagoshima University Faculty of Medicine, Kagoshima, Japan

    Xing Hui Qin & Shuji Izumo

  3. Division of Neurology, Fujimoto Hospital, Fujimoto, Japan

    Ryuichi Okubo & Hitoshi Arata

  4. Department of Neurology, Okayama University School of Medicine, Okayama, Japan

    Koji Abe

  5. Department of Neurology, Osaka University School of Medicine, Osaka, Japan

    Kei Fukada & Saburo Sakoda

  6. Department of Clinical Pathology, Osaka Medical College, Osaka, Japan

    Akira Shimizu

  7. Department of Neurology and Gerontology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji, Kamikyo-ku, 602-0841, Kyoto, Japan

    Masanori Nakagawa

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  1. Takayo Arisato
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  2. Ryuichi Okubo
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Correspondence to Masanori Nakagawa.

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Arisato, T., Okubo, R., Arata, H. et al. Clinical and pathological studies of familial amyotrophic lateral sclerosis (FALS) with SOD1 H46R mutation in large Japanese families. Acta Neuropathol 106, 561–568 (2003). https://doi.org/10.1007/s00401-003-0763-5

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  • DOI: https://doi.org/10.1007/s00401-003-0763-5

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