Lo Harriet P, Cooper Sandra T, Evesson Frances J, Seto Jane T, Chiotis Maria, Tay Valerie, Compton Alison G, Cairns Anita G, Corbett Alistair, MacArthur Daniel G, Yang Nan, Reardon Katrina, North Kathryn N
Institute for Neuromuscular Research, The Children's Hospital at Westmead, Sydney, Australia.
Neuromuscul Disord. 2008 Jan;18(1):34-44. doi: 10.1016/j.nmd.2007.08.009. Epub 2007 Sep 25.
We characterized the frequency of limb-girdle muscular dystrophy (LGMD) subtypes in a cohort of 76 Australian muscular dystrophy patients using protein and DNA sequence analysis. Calpainopathies (8%) and dysferlinopathies (5%) are the most common causes of LGMD in Australia. In contrast to European populations, cases of LGMD2I (due to mutations in FKRP) are rare in Australasia (3%). We have identified a cohort of patients in whom all common disease candidates have been excluded, providing a valuable resource for identification of new disease genes. Cytoplasmic localization of dysferlin correlates with fiber regeneration in a subset of muscular dystrophy patients. In addition, we have identified a group of patients with unidentified forms of LGMD and with markedly abnormal dysferlin localization that does not correlate with fiber regeneration. This pattern is mimicked in primary caveolinopathy, suggesting a subset of these patients may also possess mutations within proteins required for membrane targeting of dysferlin.
我们通过蛋白质和DNA序列分析，对76名澳大利亚肌肉萎缩症患者队列中的肢带型肌营养不良（LGMD）亚型频率进行了特征分析。钙蛋白酶病（8%）和dysferlin病（5%）是澳大利亚LGMD最常见的病因。与欧洲人群不同，LGMD2I（由FKRP突变引起）病例在澳大拉西亚地区很少见（3%）。我们已经确定了一组患者，其中所有常见的致病候选因素都已被排除，这为鉴定新的致病基因提供了宝贵资源。dysferlin的细胞质定位与一部分肌肉萎缩症患者的纤维再生相关。此外，我们还确定了一组患有未明确形式LGMD且dysferlin定位明显异常且与纤维再生无关的患者。这种模式在原发性小窝蛋白病中也有体现，表明这些患者中的一部分可能在dysferlin膜靶向所需的蛋白质中也存在突变。
