Poppe M, Cree L, Bourke J, Eagle M, Anderson L V B, Birchall D, Brockington M, Buddles M, Busby M, Muntoni F, Wills A, Bushby K
Institute of Human Genetics, the University Newcastle upon Tyne, UK.
Neurology. 2003 Apr 22;60(8):1246-51. doi: 10.1212/01.wnl.0000058902.88181.3d.
Mutations in the fukutin-related protein gene FKRP cause limb-girdle muscular dystrophy (LGMD2I) as well as a form of congenital muscular dystrophy (MDC1C).
To define the phenotype in LGMD2I.
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.
Thirteen patients, most with adult presentation, were homozygous for the common C826A mutation in FKRP. 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.
LGMD2I due to FKRP mutations appears to be a relatively common cause of LGMD, with respiratory and cardiac failure as prominent complications.
福金相关蛋白基因（FKRP）突变可导致肢带型肌营养不良（LGMD2I）以及一种先天性肌营养不良（MDC1C）。
明确LGMD2I的表型。
作者评估了14个携带FKRP基因突变的LGMD家庭中的16例患者，并收集了突变分析、蛋白质研究以及呼吸和心脏检查结果。
13例患者（多数为成人起病）为FKRP常见C826A突变的纯合子。另外3例为C826A的复合杂合子，其中2例儿童起病，病情进展更快。肌肉受累模式常包括小腿肥大，与肌营养不良蛋白病相似。LGMD2I患者并发症常见，有时与骨骼肌受累程度不成比例。6例患者有心脏受累，10例有呼吸功能损害：5例需要夜间呼吸支持。所有患者血清肌酸激酶至少为正常水平的5至70倍。肌肉活检中最一致的蛋白质异常是仅在肌肉切片或免疫印迹上出现层粘连蛋白α2免疫标记减少。
由FKRP突变引起的LGMD2I似乎是LGMD相对常见的病因，呼吸和心力衰竭是突出并发症。
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