Hansen Jakob, Svenstrup Kirsten, Ang Debbie, Nielsen Marit N, Christensen Jane H, Gregersen Niels, Nielsen Jørgen E, Georgopoulos Costa, Bross Peter
Research Unit for Molecular Medicine, Faculty of Health Sciences Aarhus University Hospital , Skejby Sygehus, Brendstrupgaardsvej, 8200, Aarhus N, Denmark,
J Neurol. 2007 Jul;254(7):897-900. doi: 10.1007/s00415-006-0470-y. Epub 2007 Apr 10.
A mutation in the HSPD1 gene has previously been associated with an autosomal dominant form of spastic paraplegia in a French family. HSPD1 encodes heat shock protein 60, a molecular chaperone involved in folding and quality control of mitochondrial proteins. In the present work we have investigated 23 Danish index patients with hereditary spastic paraplegia (HSP) for mutations in the HSPD1 gene. One patient was found to be heterozygous for a c.1381C > G missense mutation encoding the mutant heat shock protein 60 p.Gln461Glu. The mutation was also present in two unaffected brothers, but absent in 400 unrelated Danish individuals. We found that the function of the p.Gln461Glu heat shock protein 60 was mildly compromised. The c.1381C > G mutation likely represents a novel low-penetrance HSP allele.
先前在一个法国家庭中发现，HSPD1基因的突变与常染色体显性遗传形式的痉挛性截瘫有关。HSPD1编码热休克蛋白60，这是一种参与线粒体蛋白质折叠和质量控制的分子伴侣。在本研究中，我们调查了23名患有遗传性痉挛性截瘫（HSP）的丹麦索引患者的HSPD1基因突变情况。发现一名患者为c.1381C>G错义突变的杂合子，该突变编码突变型热休克蛋白60 p.Gln461Glu。两名未受影响的兄弟也存在该突变，但在400名无亲缘关系的丹麦个体中未发现。我们发现p.Gln461Glu热休克蛋白60的功能受到轻度损害。c.1381C>G突变可能代表一种新的低外显率HSP等位基因。
