Characterisation of a novel human neuromuscular disease associated with deficiency of the syntrophins and dystrobrevin.

肌营养不良症是一组遗传性肌肉疾病，可导致严重和进行性肌肉无力。患有肌肉萎缩症的儿童有严重且日益恶化的残疾；许多人无法行走，在严重的情况下，这种虚弱损害了呼吸肌肉，导致幼年死亡。更常见的肌肉萎缩症出现在儿童早期；然而，某些形式的肌肉萎缩症非常严重，在出生时肌肉无力很明显，受影响的婴儿永远无法充分呼吸，并在生命的最初几周内死亡。目前尚无具体的治疗方法。直到最近，导致大多数肌肉萎缩症病例的潜在基因和蛋白质异常尚不清楚，因此无法进行明确的诊断和产前诊断。我们最近在15名患有严重虚弱的儿童中发现了一组肌肉蛋白，即syntrophins和dystrobrevin的缺乏，这些儿童的病因以前是未知的。这组患者是一种新型神经肌肉疾病的第一例。我们现在将确定这些患者的致病基因突变，并确定这些肌肉蛋白的异常如何导致肌肉无力和变性。这项研究将立即应用于临床实践，因为我们将能够为儿童家庭提供有关未来后代风险的准确信息，并提供产前诊断。此外，它将提供有关人类骨骼肌正常功能的新的重要信息，可用于开发针对受影响患者的治疗方法。

The muscular dystrophies are a group of hereditary muscle diseases which can result in severe and progressive muscle weakness. Children with muscular dystrophy have significant and worsening disabilities; many are unable to walk and, in severe cases, the weakness impairs the muscles of breathing resulting in death at an early age. The more common muscular dystrophies present in early childhood; however some forms of muscular dystrophy are so severe that muscle weakness is obvious at birth, affected babies are never able to breathe adequately, and die during the first weeks of life. No specific treatment is currently available. Until recently the underlying gene and protein abnormalities resulting in the majority of cases of muscular dystrophy were unknown and hence definitive diagnosis and prenatal diagnosis was not possible. We have recently identified deficiency of a group of muscle proteins, the syntrophins and dystrobrevin, in 15 children with severe weakness, in whom the cause was previously unknown. This group of patients represent the first examples of a novel neuromuscular disorder. We will now identify the disease-causing genetic mutations in these patients and determine how abnormalities in these muscle proteins lead to muscle weakness and degeneration. This research will have immediate application to clinical practice as we will be able to give the childrens' families accurate information about the risk to future offspring and offer prenatal diagnosis. In addition, it will provide new and important information concerning the normal function of human skeletal muscle, which can be used to develop therapies for affected patients.