Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses.
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.
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroyuki
H
Ishiura
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yuji
Y
Takahashi
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Toshihiro
T
Hayashi
Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
Kayoko
K
Saito
Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, Japan.
Hirokazu
H
Furuya
Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Aomori, Japan.
Mitsunori
M
Watanabe
Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
Miho
M
Murata
Department of Neurology, Higashisaitama Hospital, National Hospital Organization, Saitama, Japan.
Mikiya
M
Suzuki
Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Akira
A
Sugiura
1] 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.
Setsu
S
Sawai
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kazumoto
K
Shibuya
1] Department of Neurology, Chigasaki Municipal Hospital, Kanagawa, Japan [2] Department of Neurology, Yokohama City University School of Medicine, Kanagawa, Japan.
Naohisa
N
Ueda
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yaeko
Y
Ichikawa
Graduate School, International University of Health and Welfare, Tokyo, Japan.
Ichiro
I
Kanazawa
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Jun
J
Goto
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Shoji
S
Tsuji
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D003710:Demography; D005190:Family; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult