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J Hum Genet. 2014 Mar;59(3):163-72. doi: 10.1038/jhg.2013.139. Epub 2014 Jan 23.

Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.

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  • 1Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 2Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
  • 3Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, Japan.
  • 4Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Aomori, Japan.
  • 5Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
  • 6Department of Neurology, Higashisaitama Hospital, National Hospital Organization, Saitama, Japan.
  • 7Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
  • 81] Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan [2] Division of Laboratory Medicine and Clinical Genetics, Chiba University Hospital, Chiba, Japan.
  • 9Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • 101] Department of Neurology, Chigasaki Municipal Hospital, Kanagawa, Japan [2] Department of Neurology, Yokohama City University School of Medicine, Kanagawa, Japan.
  • 11Graduate School, International University of Health and Welfare, Tokyo, Japan.


Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because >30 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP.

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