The phenotype of limb-girdle muscular dystrophy type 2I
The phenotype of limb-girdle muscular dystrophy type 2I
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DOI：
10.1212/01.wnl.0000058902.88181.3d
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发表时间：
2003-04-22
期刊：
影响因子：
9.9
通讯作者：
Bushby, K
中科院分区：
文献类型：
--
作者：
Poppe, M;Cree, L;Bushby, K
背景资料：fukutin相关蛋白基因FKRP的突变导致肢带型肌营养不良症（LGMD2I）以及一种先天性肌营养不良症（MDC1C）。目的：明确LGMD 2I的表型。研究方法：作者评估了来自14个家族的16名FKRP基因突变和LGMD患者，并收集了突变分析、蛋白质研究以及呼吸和心脏检查的结果。结果：13例患者，大多数与成人的表现，是纯合子的常见C826A突变FYRP。另外3例为C826A复合杂合子，其中2例在儿童期出现，病情进展更严重。肌肉受累的模式，经常包括小腿肥大，与肌营养不良症相似。LGMD2I患者的并发症很常见，有时与骨骼肌受累不成比例。6名患者有心脏受累，10名患者有呼吸障碍：5名患者需要夜间呼吸支持。所有患者的血清肌酸激酶至少为正常值的5至70倍。在肌肉活检中发现的最一致的蛋白质异常是层粘连蛋白α 2免疫标记的减少，无论是在肌肉切片上还是单独的免疫印迹。结论：FKRP突变导致的LGMD2I似乎是LGMD的一个相对常见的原因，呼吸和心力衰竭是主要的并发症。
Background: Mutations in the fukutin-related protein gene FKRP cause limb-girdle muscular dystrophy (LGMD2I) as well as a form of congenital muscular dystrophy (MDC1C). Objective: To define the phenotype in LGMD2I. Methods: The authors assessed 16 patients from 14 families with FKRP gene mutations and LGMD and collected the results of mutation analysis, protein studies, and respiratory and cardiac investigations. Results: Thirteen patients, most with adult presentation, were homozygous for the common C826A mutation in FYRP. The three other cases were compound heterozygotes for C826A and two of them presented in childhood, with more progressive disease. The pattern of muscle involvement, frequently including calf hypertrophy, was similar to dystrophinopathy. Complications in patients with LGMD2I were common and sometimes out of proportion to the skeletal muscle involvement. Six patients had cardiac involvement, and 10 had respiratory impairment: five required nocturnal respiratory support. All patients had serum creatine kinase at least 5 to 70 times normal. The most consistent protein abnormality found on muscle biopsy was a reduction of laminin alpha2 immunolabeling, either on muscle sections or immunoblotting alone. Conclusions: LGMD2I due to FKRP mutations appears to be a relatively common cause of LGMD, with respiratory and cardiac failure as prominent complications.