Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia.
Evidence that paternal expression of the epsilon-sarcoglycan gene accounts for reduced penetrance in myoclonus-dystonia.
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有证据表明，ε-肌聚糖基因的父系表达导致肌阵挛肌张力障碍外显率降低。
DOI：
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发表时间：
2002
影响因子：
9.8
通讯作者：
C. Klein
中科院分区：
文献类型：
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作者：
B. Müller;K. Hedrich;N. Kock;N. Dragasevic;M. Svetel;J. Garrels;O. Landt;M. Nitschke;P. Pramstaller;W. Reik;E. Schwinger;J. Sperner;L. Ozelius;V. Kostic;C. Klein
肌阵挛-肌张力障碍(M-D)是一种以肌肉快速收缩、持续扭转和重复运动为特征的运动障碍，最近被认为与epsilon-肌聚糖基因(SGCE)的突变有关。遗传方式为常染色体显性遗传，母系遗传外显率降低，提示母系印记机制。我们提出一个明显的散发性多发性骨髓瘤病例和两个来自常染色体隐性遗传的多发性硬化症家族的患者。在这两个家庭中，我们都检测到了一种常染色体显性遗传的SGCE突变，该突变来自患者临床上未受影响的父亲。然而，在第一个家系中，RNA表达研究显示在受影响的个体中只表达突变的等位基因，而在未受影响的突变携带者中仅表达正常等位基因，而第二个家系中的受影响个体同时表达两种等位基因。此外，我们还发现SGCE基因启动子区域的差异甲基化区域是印记基因的特征。在一个未受M-D影响的家系中，使用启动子区域罕见的多态作为标记，我们证明了母体等位基因的甲基化，这与SGCE基因的母体印记一致。在具有SGCE基因双等位基因表达的M-D患者中，印迹的丢失与几个CpG二核苷酸部分甲基化的丢失有关。
Myoclonus-dystonia (M-D) is a movement disorder characterized by rapid muscle contractions and sustained twisting and repetitive movements and has recently been associated with mutations in the epsilon-sarcoglycan gene (SGCE). The mode of inheritance is autosomal dominant with reduced penetrance upon maternal transmission, suggesting a putative maternal imprinting mechanism. We present an apparently sporadic M-D case and two patients from an M-D family with seemingly autosomal recessive inheritance. In both families, we detected an SGCE mutation that was inherited from the patients' clinically unaffected fathers in an autosomal dominant fashion. Whereas, in the first family, RNA expression studies revealed expression of only the mutated allele in affected individuals and expression of the normal allele exclusively in unaffected mutation carriers, the affected individual of the second family expressed both alleles. In addition, we identified differentially methylated regions in the promoter region of the SGCE gene as a characteristic feature of imprinted genes. Using a rare polymorphism in the promoter region in a family unaffected with M-D as a marker, we demonstrated methylation of the maternal allele, in keeping with maternal imprinting of the SGCE gene. Loss of imprinting in the patient with M-D who had biallelic expression of the SGCE gene was associated with partial loss of methylation at several CpG dinucleotides.
肌阵挛-肌张力障碍的主要位点定位于 8 个家族的 7q 染色体。
影响因子：
9.8
作者：
Klein,C;Schilling,K;Saunders-Pullman,RJ;Garrels,J;Breakefield,XO;Brin,MF;deLeon,D;Doheny,D;Fahn,S;Fink,JS;Forsgren,L;Friedman,J;Frucht,S;Harris,J;Holmgren,G;Kis,B;Kurlan,R;Kyllerman,M;Lang,AE;Leung,J;Raymond,D
通讯作者：
Raymond,D