Heydemann Ahlke, Doherty Katherine R, McNally Elizabeth M
Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL 60637, USA.
Biochim Biophys Acta. 2007 Feb;1772(2):216-28. doi: 10.1016/j.bbadis.2006.06.013. Epub 2006 Jul 11.
The genetic understanding of the muscular dystrophies has advanced considerably in the last two decades. Over 25 different individual genes are now known to produce muscular dystrophy, and many different "private" mutations have been described for each individual muscular dystrophy gene. For the more common forms of muscular dystrophy, phenotypic variability can be explained by precise mutations. However, for many genetic mutations, the presence of the identical mutation is associated with marked phenotypic range that affects muscle function as well as cardiac function. The explanation for phenotype variability in the muscular dystrophies is only now being explored. The availability of genetically engineered animal models has allowed the generation of single mutations on the background of highly inbred strain. Phenotypic variation that is altered by genetic background argues for the presence of genetic modifier loci that can ameliorate or enhance aspects of the dystrophic phenotype. A number of individual genes have been implicated as modifiers of muscular dystrophy by studies in genetically engineered mouse models of muscular dystrophy. The value of these genes and products is that the pathways identified through these experiments may be exploited for therapy.
在过去二十年里，对肌营养不良症的遗传学认识有了显著进展。目前已知超过25种不同的个体基因会导致肌营养不良症，并且针对每个个体的肌营养不良症基因都描述了许多不同的“私人”突变。对于更常见的肌营养不良症形式，表型变异性可以通过精确的突变来解释。然而，对于许多基因突变，相同突变的存在与显著的表型范围相关，这会影响肌肉功能以及心脏功能。目前才开始探索肌营养不良症中表型变异性的解释。基因工程动物模型的可用性使得能够在高度近交系的背景下产生单一突变。由遗传背景改变的表型变异表明存在可以改善或增强营养不良表型各方面的遗传修饰位点。通过对基因工程肌营养不良小鼠模型的研究，一些个体基因已被认为是肌营养不良症的修饰基因。这些基因和产物的价值在于，通过这些实验确定的途径可能被用于治疗。
