Mutations in the sarcoglycan genes in patients with myopathy
Mutations in the sarcoglycan genes in patients with myopathy
复制标题
DOI：
10.1056/nejm199702273360904
复制
发表时间：
1997-02-27
影响因子：
158.5
通讯作者：
Kunel, RW
中科院分区：
文献类型：
--
作者：
Duggan, DJ;Gorospe, JR;Kunel, RW
背景一些常染色体隐性肢带型肌营养不良患者编码肌聚糖蛋白（α-、β-、γ-和δ-肌聚糖）的基因发生突变。为了确定肌聚糖基因突变的频率和临床特征和基因型之间的关系，我们研究了几百例myopathy.Methods抗体对α-肌聚糖染色肌肉活检标本556例肌病和正常dystrophin基因（基因经常删除的X-连锁肌营养不良症）。结果556例患者中有54例肌活检标本的α-肌聚糖水平在免疫组化染色中降低，其中54例肌活检标本的α-肌聚糖水平在免疫组化染色中降低，54例肌活检标本的α-肌聚糖水平在免疫组化染色中降低，54例肌活检标本的α-肌聚糖水平在免疫组化染色中降低（10%）;在这些患者中，有25例未检测到α-肌聚糖。对54名患者中的50名进行肌聚糖基因突变筛查，发现29名患者（58%）发生突变：17名（34%）α-肌聚糖基因突变，8名（16%）β-肌聚糖基因突变，4名（8%）γ-肌聚糖基因突变。21名患者（42%）未发现突变。肌聚糖基因突变的患病率在重度肌萎缩症患者中最高。（Duchenne样）肌营养不良症，始于童年（83名患者中有18名，占22%）;近端食管癌患者的患病率（肢带型）肌营养不良，发病较晚，结论编码肌聚糖蛋白的基因缺陷局限于Duchenne样和肢端型肌萎缩侧索硬化症患者。肌营养不良蛋白正常的带状肌营养不良症，发生在11%的此类患者中。(C)1997年，马萨诸塞州医学会。
Background Some patients with autosomal recessive limb-girdle muscular dystrophy have mutations in the genes coding for the sarcoglycan proteins (alpha-, beta-, gamma-, and delta-sarcoglycan). To determine the frequency of sarcoglycan-gene mutations and the relation between the clinical features and genotype, we studied several hundred patients with myopathy.Methods Antibody against alpha-sarcoglycan was used to stain muscle-biopsy specimens from 556 patients with myopathy and normal dystrophin genes (the gene frequently deleted in X-linked muscular dystrophy). Patients whose biopsy specimens showed a deficiency of alpha-sarcoglycan on immunostaining were studied for mutations of the alpha-, beta-, and gamma-sarcoglycan genes with reverse transcription of muscle RNA, analysis involving single-strand conformation polymerphisms, and sequencing,Results Levels of alpha-sarcoglycan were found to be decreased on immunostaining of muscle-biopsy specimens from 54 of the 556 patients (10 percent); in 25 of these patients no alpha-sarcoglycan was detected. Screening for sarcoglycan-gene mutations in 50 of the 54 patients revealed mutations in 29 patients (58 percent): 17 (34 percent) had mutations in the alpha-sarcoglycan gene, 8 (16 percent) in the beta-sarcoglycan gene, and 4 (8 percent) in the gamma-sarcoglycan gene. No mutations were found in 21 patients (42 percent). The prevalence of sarcoglycan-gene mutations was highest among patients with severe (Duchenne-like) muscular dystrophy that began in childhood (18 of 83 patients, or 22 percent); the prevalence among patients with proximal (limb-girdle) muscular dystrophy with a later onset was 6 percent (11 of 180 patients).Conclusions Defects in the genes coding for the sarcoglycan proteins are limited to patients with Duchenne-like and limb-girdle muscular dystrophy with normal dystrophin and occur in 11 percent of such patients. (C) 1997, Massachusetts Medical Society.