Molecular genetics of familial spastic paraplegia

家族性痉挛性截瘫的分子遗传学

• 批准号: 12670597
• 负责人: KOBAYASHI Hisashi
• 金额: $ 2.18万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670597/
• 关键词: 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

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.

遗传性痉挛性截瘫（HSP）是一组罕见的疾病，其特点是巨大的临床和遗传异质性。迄今为止，9个常染色体显性HSP位点，3个X连锁HSP位点，4个常染色体隐性HSP位点已被确定。我们对13个日本常染色体隐性遗传HSP家族进行了临床特征分析和遗传连锁分析。13个家庭均属于“复杂”类型，表现为智力障碍和胼胝体变薄。排除了与8 p12-q13和16 qter位点的连锁，而13个家庭中有10个显示与15 q13 -15连锁的标记数据一致。与15号染色体连锁的10个家系在D15 S994和D15 S659两侧的3cM区段中的多点LOD得分均在9.00以上，在D15 S994至D15 S659的1.2cM端粒位置处的多点LOD得分最高，为9.68。我们已经证明，ARHSP与TCC，隐性痉挛性截瘫的亚型映射到染色体15 q13 -15。我们没有发现任何连锁不平衡ARHSP与TCC和标记位点在我们的研究中使用。由于标记位于0.5 cM的间隔在研究中，使用更密集的标记将需要进一步调查的连锁不平衡。

项目成果

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 autosoma

柴崎 Y、田中 H、岩渊 K、川崎 S、近藤 H、上川 K、上田 M、神谷 T、片山 Y、中村 A、高岛 H、中川 M、增田 M、内海 H、中室 T、多田 K、黑原 K

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)

Wakabayashi K、Kobayashi H、Kawasaki S、Kondo H、Takahashi H.：“常染色体隐性遗传性痉挛性截瘫伴胼胝体发育不全、多系统变性和泛素化嗜酸性颗粒”《神经病理学报》。

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.:

柴崎 Y.、田中 H.、岩渊 K.、川崎 S.、近藤 H.。

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 (200

Wakabayashi K.、Kobayashi H.、Kawasaki S.、Kondo H.、Takahashi H.：“常染色体隐性遗传性痉挛性截瘫伴胼胝体发育不全、多系统变性和泛素化嗜酸性粒细胞”Acta Neuropathol (Berl) Jan. 101 (1)。

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)

Wakabayashi K、Kobayashi H、Kawasaki S、Kondo H、Takahashi H.：“常染色体隐性遗传性痉挛性截瘫伴胼胝体发育不良、多系统变性和泛素化嗜酸性粒细胞”Acta Neuropathol (Berl)。