Thornton C A, Johnson K, Moxley R T
Department of Neurology, University of Rochester Medical Center, NY 14642.
Ann Neurol. 1994 Jan;35(1):104-7. doi: 10.1002/ana.410350116.
The genetic basis of myotonic dystrophy is an unstable expansion of CTG repeats located in a gene on chromosome 19 that encodes a putative serine/threonine protein kinase. We studied the somatic mosaicism of the (CTG)n expansion in myotonic dystrophy patients. (CTG)n expansions were 2- to 13-fold greater in DNA isolated from skeletal muscle than in DNA from leukocytes in 10 of 11 patients with myotonic dystrophy. Different muscles of the same individual showed similar (CTG)n expansions. In postmortem tissues from an adult patient, (CTG)n expansions in brain, skeletal muscle, cardiac muscle, testes, and liver were all greater than in leukocytes. Normal myotonic dystrophy gene alleles from 7 healthy subjects had the same number of CTG repeats in leukocytes and muscle. The myotonic dystrophy mutation displays pronounced heterogeneity in somatic cells. The (CTG)n expansion observed in peripheral blood leukocytes is not necessarily representative of the repeat expansion in affected tissues, such as skeletal muscle and myocardium. In some patients with myotonic dystrophy, the predictive value of genetic analysis based on leukocyte DNA may be limited.
强直性肌营养不良的遗传基础是位于19号染色体上一个基因中的CTG重复序列不稳定扩增，该基因编码一种假定的丝氨酸/苏氨酸蛋白激酶。我们研究了强直性肌营养不良患者中(CTG)n扩增的体细胞镶嵌现象。在11例强直性肌营养不良患者中的10例中，从骨骼肌分离的DNA中(CTG)n扩增比白细胞DNA中的扩增高2至13倍。同一个体的不同肌肉显示出相似的(CTG)n扩增。在一名成年患者的尸检组织中，脑、骨骼肌、心肌、睾丸和肝脏中的(CTG)n扩增均大于白细胞中的扩增。7名健康受试者的正常强直性肌营养不良基因等位基因在白细胞和肌肉中的CTG重复序列数量相同。强直性肌营养不良突变在体细胞中表现出明显的异质性。在外周血白细胞中观察到的(CTG)n扩增不一定代表受影响组织（如骨骼肌和心肌）中的重复扩增。在一些强直性肌营养不良患者中，基于白细胞DNA的遗传分析的预测价值可能有限。
