Anttonen Anna-Kaisa, Mahjneh Ibrahim, Hämäläinen Riikka H, Lagier-Tourenne Clotilde, Kopra Outi, Waris Laura, Anttonen Mikko, Joensuu Tarja, Kalimo Hannu, Paetau Anders, Tranebjaerg Lisbeth, Chaigne Denys, Koenig Michel, Eeg-Olofsson Orvar, Udd Bjarne, Somer Mirja, Somer Hannu, Lehesjoki Anna-Elina
Folkhälsan Institute of Genetics and Neuroscience Center, University of Helsinki, PO Box 63, FI-00014 Helsinki, Finland.
Nat Genet. 2005 Dec;37(12):1309-11. doi: 10.1038/ng1677. Epub 2005 Nov 13.
We identified the gene underlying Marinesco-Sjögren syndrome, which is characterized by cerebellar ataxia, progressive myopathy and cataracts. We identified four disease-associated, predicted loss-of-function mutations in SIL1, which encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5. These data, together with the similar spatial and temporal patterns of tissue expression of Sil1 and Hspa5, suggest that disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sjögren syndrome.
我们鉴定出了马-约二氏综合征（Marinesco-Sjögren syndrome）的致病基因，该综合征的特征为小脑共济失调、进行性肌病和白内障。我们在SIL1基因中鉴定出4个与疾病相关的、预测会导致功能丧失的突变，SIL1基因编码热休克蛋白70（HSP70）伴侣蛋白HSPA5的核苷酸交换因子。这些数据，连同Sil1和Hspa5在组织表达上相似的时空模式，表明SIL1-HSPA5相互作用紊乱和蛋白质折叠异常是马-约二氏综合征的主要病理机制。
