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

• Published in: Journal of human genetics Vol. 59; no. 3; pp. 163 - 172
• Main Authors: Ishiura, Hiroyuki, Takahashi, Yuji, Hayashi, Toshihiro, Saito, Kayoko, Furuya, Hirokazu, Watanabe, Mitsunori, Murata, Miho, Suzuki, Mikiya, Sugiura, Akira, Sawai, Setsu, Shibuya, Kazumoto, Ueda, Naohisa, Ichikawa, Yaeko, Kanazawa, Ichiro, Goto, Jun, Tsuji, Shoji
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2014
• Subjects: Adolescent; Adult; Asian Continental Ancestry Group - genetics; Base Sequence; Child; Child, Preschool; Comparative Genomic Hybridization; Demography; Diagnosis; DNA Mutational Analysis; Epidemiology; Family; Female; Hereditary spastic paraplegia; Humans; Hybridization; Japan - epidemiology; Male; Middle Aged; Molecular Epidemiology; Molecular Sequence Data; Mutation; Mutation - genetics; Myelin proteolipid protein; Neurodegenerative diseases; Oligonucleotide Array Sequence Analysis; Paralysis; Sequence Deletion - genetics; Spastic Paraplegia, Hereditary - epidemiology; Spastic Paraplegia, Hereditary - genetics; Spasticity; Young Adult; Japan
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2013.139

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.