RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene
RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene
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DOI：
10.1136/jmg.2003.014274
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发表时间：
2004-03-01
影响因子：
4
通讯作者：
Robinson, R
中科院分区：
文献类型：
--
作者：
Shepherd, S;Ellis, F;Robinson, R
先天性肌病是一组难以区分的疾病。诊断通常依赖于肌肉活检标本的组织学检查结果，并结合临床诊断。在不同的先天性肌病的临床特征有显著程度的重叠：鉴定遗传决定因素可能因此有助于建立一个坚定的诊断。中心性肌病（CCD）是一种罕见的先天性肌病。组织学上，使用氧化酶染色，通过中心核心的丰度来识别，其特征是线粒体耗竭的局部区域和1型骨骼肌纤维中特有的肌节解体，并延伸到整个长度。芯通常是中心和唯一的，但也可能是偏心的或在一根纤维中有多个芯。受影响的患者可能表现为先天性肌肉张力低下，明显的近端无力，运动发育迟缓，肌酸激酶（CK）水平轻微升高。此外，骨骼异常，如先天性髋关节移位和脊柱侧凸是常见的。在生命的后期，肌肉力量可能会改善，但在极少数情况下，观察到进行性肌肉无力。呼吸功能不全是罕见的。总的来说，这种疾病表现出显著的表型变异性；在一项13例病例的研究中，有组织学症状的患者中，临床上无症状的患者高达40%。3
The congenital myopathies are a group of disorders that are difficult to distinguish. Diagnosis is frequently dependent on the result of histological examination of muscle biopsy specimens in conjunction with clinical diagnosis. There is a significant degree of overlap in the clinical features of different congenital myopathies: identification of genetic determinants may therefore aid in establishing a firm diagnosis.Central core disease (CCD) is a rare congenital myopathy. Histologically, using oxidative enzyme stains, it is identified by the abundance of central cores, characterised by localised areas of mitochondrial depletion and sarcomere disorganization exclusively in type 1 skeletal muscle fibres, and extending throughout their length. Cores are often central and unique, but may be eccentric or multiple within one fibre. Affected patients may present with congenital muscle hypotonia, pronounced proximal weakness, delayed motor development, and slightly elevated creatine kinase (CK) levels. In addition, skeletal anomalies such as congenital hip displacement and scoliosis are frequent. Later in life muscle strength may improve, but in rare cases progressive muscle weakness is observed. Respiratory insufficiency is rare. 1 2 Overall, the disorder demonstrates significant phenotypic variability; in a study of 13 cases, as many as 40% of patients with histological signs of disease were clinically asymptomatic. 3