CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.
CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.
复制标题
常染色体显性遗传家族性痉挛性截瘫中的 CAG 重复扩张：部分患者的新扩张。
DOI：
10.1093/hmg/7.11.1779
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发表时间：
1998
影响因子：
3.5
通讯作者：
Bird,TD
中科院分区：
文献类型：
--
作者：
Benson,KF;Horwitz,M;Wolff,J;Friend,K;Thompson,E;White,S;Richards,RI;Raskind,WH;Bird,TD
常染色体显性遗传家族性痉挛性截瘫（Autosomal dominant familial spastic paraplegia，FSP）是一种遗传异质性神经退行性疾病，有3个基因位点被定位于染色体14q11.2-q24.3（SPG 3）、2 p21-p24（SPG 4）和15q11.1（SPG 6）。重复扩增检测（RED）方法已被用于证明在一些FSP家族中扩增的CAG重复序列映射到SPG 4。我们分析了20个FSP家族，其中包括4个与SPG 4连锁的家族，发现在大多数情况下，RED检测到的重复扩增是由于染色体18q21.1SEF2- 1或17q21.3ERDA1位点的非致病性扩增。SEF 2 - 1和ERDA 1的多态性扩增似乎很频繁，可能会混淆RED研究，以寻找导致预期疾病的基因。然而，在6个FSP家族中，CAG重复扩增在一个受影响的和有风险的个体中检测到，这不是SEF 2 - 1和ERDA 1位点扩增的结果。总的来说，37例CAG/CTG重复扩增的FSP患者中有11例（30%）的SEF 2 - 1和ERDA 1基因座无法解释，相比之下，23例未受影响的高危个体中有2例（9%），19例对照组中没有一例。在大多数情况下，这些新的扩张比以前报告的要短。
Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2–q24.3 (SPG3), 2p21–p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1SEF2-1or 17q21.3ERDA1locus. Polymorphic expansions atSEF2-1andERDA1appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of theSEF2-1andERDA1loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by theSEF2-1andERDA1loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.