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。有些类型导致受影响儿童过早死亡，而其他类型则与成年生活相适应。像任何儿童疾病一样，先天性肌病对有关家庭造成相当大的创伤。有可能生育另一个受影响孩子的夫妇往往要等到产前诊断出他们的特殊疾病后才试图生育更多的孩子。然而，产前诊断只有在确定了导致疾病的基因和个体家庭的突变后才有可能。过去，参与该项目的实验室，珀斯澳大利亚神经肌肉研究所的分子神经遗传学实验室和悉尼新儿童医院的神经遗传学研究部门，已经确定了先天性肌病的疾病基因。现在可以对已确定致病突变的家庭进行产前诊断。然而，许多先天性肌病的遗传原因尚不清楚。DNA和其他样本已被送到世界各地的实验室，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利亚样本，以确定其他先天性肌病基因。这将帮助目前无法进行产前诊断的家庭。发现这些基因还可以通过澄清哪些蛋白质参与其中来增加对疾病的了解。在项目的第二部分，我们将研究突变蛋白，试图揭示基因突变是如何导致疾病的。该项目的第三部分是在疾病基因已知的情况下，重新评估先天性肌病中高度可变的肌肉病理，以研究基因型-表型相关性。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.