Background Hereditary spastic paraplegia （HSP） is a group of inherited neurodegenerative disorders with the shared characteristics of slowly progressive spasticity and weakness of the lower limbs. Thirteen loci for ...Background Hereditary spastic paraplegia （HSP） is a group of inherited neurodegenerative disorders with the shared characteristics of slowly progressive spasticity and weakness of the lower limbs. Thirteen loci for autosomal dominant HSP have been mapped. Methods A Chinese family with HSP was found in the Shandong province and Inner Mongolia Autonomous Region of China and genomic DNA of all 19 family members was isolated. After exclusion of known autosomal dominant loci, a genome wide scan and linkage analysis were performed. Results The known autosomal dominant loci of SPG3A, SPG4, SPG6, SPG8, SPG9, SPG10, SPG12, SPG13, SPG17, SPG19, SPG29, SPG31 and SPG33 were excluded by linkage analysis. The results of a genome wide scan demonstrated candidate linkage to a locus on chromosome 11 p14.1-p11.2, over an 18.88 cM interval between markers D11 S1324 and D11 S1933. A maximal, two point LOD score of 2.36 for marker D11S935 at a recombination fraction （e） of 0 and a multipoint LOD score of 2.36 for markers D11S1776, D11S1751, D11S1392, D11S4203, D11S935, D11S4083, and D11S4148 at θ=0, suggest linkage to this locus. Conclusion The HSP neuropathy in this family may represent a novel genetic entity, which will facilitate discovery of this causative gene.展开更多
基金This work was supported by grants from the National High Technology Research and Development Program of China （＂863＂ Program） （No. 2004AA227040）, the National Key Health Research Project Foundation of China during the 10th Five-Year Plan Period （No. 2004BA720A03） and the National Natural Science Foundation of China （No. 30300199 and No. 30671151）.
文摘Background Hereditary spastic paraplegia （HSP） is a group of inherited neurodegenerative disorders with the shared characteristics of slowly progressive spasticity and weakness of the lower limbs. Thirteen loci for autosomal dominant HSP have been mapped. Methods A Chinese family with HSP was found in the Shandong province and Inner Mongolia Autonomous Region of China and genomic DNA of all 19 family members was isolated. After exclusion of known autosomal dominant loci, a genome wide scan and linkage analysis were performed. Results The known autosomal dominant loci of SPG3A, SPG4, SPG6, SPG8, SPG9, SPG10, SPG12, SPG13, SPG17, SPG19, SPG29, SPG31 and SPG33 were excluded by linkage analysis. The results of a genome wide scan demonstrated candidate linkage to a locus on chromosome 11 p14.1-p11.2, over an 18.88 cM interval between markers D11 S1324 and D11 S1933. A maximal, two point LOD score of 2.36 for marker D11S935 at a recombination fraction （e） of 0 and a multipoint LOD score of 2.36 for markers D11S1776, D11S1751, D11S1392, D11S4203, D11S935, D11S4083, and D11S4148 at θ=0, suggest linkage to this locus. Conclusion The HSP neuropathy in this family may represent a novel genetic entity, which will facilitate discovery of this causative gene.
