11号染色体p14.1 - p11.2上一个新的常染色体显性遗传性痉挛性截瘫候选基因座。

A novel candidate locus on chromosome 11p14.1-p11.2 for autosomal dominant hereditary spastic paraplegia.

作者信息

Zhao Guo-hua, Hu Zheng-mao, Shen Lu, Jiang Hong, Ren Zhi-jun, Liu Xiao-min, Xia Kun, Guo Peng, Pan Qian, Tang Bei-sha

机构信息

Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

出版信息

Chin Med J (Engl). 2008 Mar 5;121(5):430-4.

PMID:18364116

Abstract

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 11p14.1-p11.2, over an 18.88 cM interval between markers D11S1324 and D11S1933. A maximal, two point LOD score of 2.36 for marker D11S935 at a recombination fraction (theta) of 0 and a multipoint LOD score of 2.36 for markers D11S1776, D11S1751, D11S1392, D11S4203, D11S935, D11S4083, and D11S4148 at theta=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.

摘要

背景

遗传性痉挛性截瘫（HSP）是一组遗传性神经退行性疾病，具有下肢缓慢进行性痉挛和无力的共同特征。已定位了13个常染色体显性遗传性痉挛性截瘫的基因座。

方法

在中国山东省和内蒙古自治区发现了一个患有遗传性痉挛性截瘫的家系，并提取了所有19名家庭成员的基因组DNA。在排除已知的常染色体显性基因座后，进行了全基因组扫描和连锁分析。

结果

通过连锁分析排除了已知的SPG3A、SPG4、SPG6、SPG8、SPG9、SPG10、SPG12、SPG13、SPG17、SPG19、SPG29、SPG31和SPG33常染色体显性基因座。全基因组扫描结果显示，在标记D11S1324和D11S1933之间的18.88 cM区间内，与11号染色体p14.1 - p11.2上的一个基因座存在候选连锁。标记D11S935在重组率（θ）为0时的最大两点LOD得分为2.36，标记D11S1776、D11S1751、D11S1392、D11S4203、D11S935、D11S4083和D11S4148在θ = 0时的多点LOD得分为2.36，提示与该基因座连锁。