Molecular genetics of familial spastic paraplegia

• Project/Area Number: 12670597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: KOBAYASHI Hisashi Brain Research Institute, Niigata University, Assistant, 脳研究所, 助手 (30303168)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: spastic paraplegia / chromosome 15q / autosomal recessive / MAP 1A / motor neurog / gene / linkage disequilibrium / founder effect / MAPIA / 痙性対麻痺 / 遺伝子 / 連鎖解析 / 運動ニューロン

Research Abstract

The hereditary spastic paraplegia (HSP) is a group of rare disorders that are characterized by great clinical and genetic heterogeneity. To date, nine loci for autosomal dominant HSP, three loci for X-linked HSP, and four loci for autosomal recessive HSP have been characterized. We have clinically characterized 13 Japanese autosomal recessive HSP families and performed genetic linkage analyzes. All the 13 families were classified as the "complicated" forms, which manifested with mental impairment and thin corpus callosum (TCC). Linkage to the 8p12-q13 and 16qter loci was excluded, while ten of the 13 families showed marker data consistent with linkage to 15q13-15. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3 cM segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 cM telomeric from D15S994 to D15S659. We have shown that ARHSP with TCC, a subtype of recessive spastic paraplegia maps to chromosome 15q13-15. We did not detect any linkage disequilibrium between ARHSP with TCC and the marker loci used in our study. Since the markers were located at 0.5 cM intervals in the study, use of more densely placed markers will be required for further investigation on the linkage disequilibrium.

Research Products

• [Publications] Shibasaki Y, Tanaka H, Iwabuchi K, Kawasaki S, Kondo H, Uekawa K, Ueda M, Kamiya T, Katayama Y, Nakamura A, Takashima H, Nakagawa M, Masuda M, Utsumi H, Nakamuro T, Tada K, Kurohara K, Inoue K, Koike F, Sakai T, Tsuji S, Kobayashi H.: "Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15q13-15"Ann Neurol. 48(1). 108-112 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wakabayashi K, Kobayashi H, Kawasaki S, Kondo H, Takahashi H.: "Autosomal recessive spastic paraplegra with hypoplastic corpus callosum, multisystem degeneration and ubiquitinated eosinophilic granules"Acta Neuropathol. 101(1). 69-73 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shibasaki Y., Tanaka H., Iwabuchi K., Kawasaki S., Kondo H,. Uekawa K., Ueda M., Kamiya T., Katayama Y., Nakamura A., Takashima H., Nakagawa M, Masuda M., Utsumi H., Nakamuro T., Tada K., Kurohara K., Inoue K., Koike F., Sakai T., Tsuji S., Kobayashi H.: "Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15q13-15"Ann Neurol Jul. 48 (1). 108-112 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wakabayashi K., Kobayashi H., Kawasaki S., Kondo H., Takahashi H.: "Autosomal recessive spastic paraplegia with hypoplastic corpus callosum, multisystem degeneration and ubiquiti nated eosinophilic granules"Acta Neuropathol (Berl) Jan. 101 (1). 69-73 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wakabayashi K, Kobayashi H, Kawasaki S, Kondo H, Takahashi H.: "Autosomal recessive spastic paraplegia with hypoplastic corpus callosum, multisystem degeneration and ubiquitinated eosinophilic granules"Acta Neuropathol (Berl). 101(1). 69-73 (2001)
• [Publications] Shibasaki Y, Tanaka H, Iwabuchi K, Kawasaki S, Kondo H, Uekawa K, Ueda M, Kamiya T, Katayama Y, Nakamura A, Takashima H, Nakagawa M, Masuda M, Utsumi H, Nakamuro T, Tada K, Kurohara K, Inoue K, Koike F, Sakai T, Tsuji S, Kobayashi H.: "Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum to chromosome 15q13-15"Ann Neurol. 48(1). 108-112 (2000)
• [Publications] Y.Shibasaki et.al.: "Linkage of autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum chromosome15g13-15"Annals of Neurology. 48. 108-112 (2000)