Molecular and Clinico-pathological Investigation of Congenital Myopathies

先天性肌病是一种遗传性疾病，从出生起就引起肌肉无力。有些类型会导致受影响儿童的过早死亡，而另一些类型则与成年生活相容。像任何儿童疾病一样，先天性肌病给有关家庭造成相当大的创伤。有另一个受影响的孩子的风险的夫妇经常等待产前诊断，以获得他们的特定疾病之前，试图有更多的孩子。然而，产前诊断只有在确定了引起疾病的基因和单个家庭中的突变后才有可能。在过去，在这个项目中合作的实验室，分子神经遗传学实验室，澳大利亚神经肌肉研究所，珀斯，和神经遗传学研究单位，新儿童医院，悉尼，已经确定了先天性肌病的疾病基因。对于那些发现致病突变的家庭，现在可以进行产前诊断。然而，许多先天性肌病的遗传原因仍然未知。来自世界各地的DNA和其他样本被送往实验室，使我们成为先天性肌病研究的参考中心。该项目的第一部分是研究这些和澳大拉西亚样本，以确定其他先天性肌病基因。这将有助于目前无法进行产前诊断的家庭。发现这些基因也通过澄清哪些蛋白质参与增加了对疾病的理解。在项目的第二部分，我们将研究突变的蛋白质，试图解开基因突变如何导致疾病。该项目的第三部分是重新评估高度可变的肌肉病理先天性肌病的情况下，疾病基因是现在已知的，以调查基因型-表型的相关性。了解先天性肌病的病理基础将最终使我们开始理性地思考可能的治疗方法。

Congenital myopathies are inherited disorders causing muscle weakness from birth. Some types lead to early death of the affected child, while others are compatible with life to adulthood. Like any disease of childhood, the congenital myopathies cause considerable trauma to the families concerned. Couples at risk of having another affected child frequently wait for prenatal diagnosis to become available for their particular disease before attempting to have further children. However, prenatal diagnosis is only possible once the gene causing a disorder and the mutation in an individual family are identified. In the past, the Laboratories collaborating in this project, the Molecular Neurogenetics Laboratory, Australian Neuromuscular Research Institute, Perth, and the Neurogenetics Research Unit, New Children s Hospital, Sydney, have identified disease genes for congenital myopathies. Prenatal diagnosis is now possible for families whose disease-causing mutation is identified. However the genetic cause of many of the congenital myopathies remains unknown. DNA and other samples have been sent to the Laboratories from around the world, making us reference centres for congenital myopathy research. Part one of the project is to study these and Australasian samples, to identify other congenital myopathy genes. This will help families who currently cannot have prenatal diagnosis. Finding the genes also increases understanding of the diseases by clarifying which proteins are involved. In part two of the project we shall study the mutated proteins, to try to unravel how the gene mutations cause the diseases. The third part of the project is to reevaluate the highly variable muscle pathology in congenital myopathies in cases where the disease gene is now known, in order to investigate genotype-phenotype correlations. Understanding the pathologic basis of the congenital myopathies will ultimately allow us to begin to think rationally about possible treatments.