Cellular and molecular studies in muscle and cultures from patients with multiple mitochondrial DNA deletions

被引:6
作者
Carrozzo, R
Davidson, MM
Walker, WF
Hirano, M
Miranda, AF
机构
[1] Columbia Univ Coll Phys & Surg, Dept Neurol, H Houston Merritt Clin Res Ctr Muscular Dystrophy, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Pathol, H Houston Merritt Clin Res Ctr Muscular Dystrophy, New York, NY 10032 USA
关键词
mitochondrial DNA; multiple deletions; muscle satellite cells; muscle culture; ophthalmoplegia;
D O I
10.1016/S0022-510X(99)00193-8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
In the last decade, several mitochondrial encephalomyopathies have been pathogenically associated with large-scale mitochondrial DNA deletions that are sporadic, or with point mutations that are maternally inherited. The mutations were also demonstrated in cultures of muscle satellite cells obtained from the patients. Subsequently, multiple deletions in mitochondrial DNA were found in several families. The affected members had progressive external ophthalmoplegia, cataracts and limb weakness, inherited as an autosomal dominant trait, or progressive external ophthalmoplegia with neurogastrointestinal encephalomyopathy or with cardiomyopathy, inherited as an autosomal recessive trait. To better understand the developmental pathobiology and localization of the multiple deletions, we performed comparative molecular genetic studies in muscle and cultures from patients. Whereas multiple deletions were found in muscle fragments from which muscle satellite cells were removed by enzymatic digestion, no deletions were found in the satellite cells or their cultured progeny. Our results suggest that multiple mitochondrial DNA deletions arise as somatic mutations during later stages of muscle development, or in terminally differentiated myofibers, (C) 1999 Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:24 / 31
页数:8
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