Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis
Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis
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DOI：
10.1016/j.ygeno.2008.01.011
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发表时间：
2008-05-01
期刊：
影响因子：
4.4
通讯作者：
Mickelson, James R.
中科院分区：
文献类型：
--
作者：
McCue, Molly E.;Valberg, Stephanie J.;Mickelson, James R.
多糖沉积性肌病（PSSM）是一种新型的糖原病，其特征是骨骼肌糖原异常积聚和肌肉损害与运动。它不同于人类和家畜中描述的由糖原分解、糖酵解和糖原合成中的已知缺陷引起的糖原贮积病。一个全基因组关联确定GYS 1，编码骨骼肌糖原合酶（GS），作为PSSM的候选基因。DNA序列分析表明，在一个高度保守的GS区的组氨酸取代的甘氨酸突变。功能分析表明，GS活性升高PSSM马，单倍型分析和等位基因年龄估计表明，这种突变是相同的马品种之间的血统。这是GYS 1功能获得性突变导致糖原累积病的首次报道。(c)2008年爱思唯尔公司All rights reserved.
Polysaccharide storage myopathy (PSSM) is a novel glycogenosis in horses characterized by abnormal glycogen accumulation in skeletal muscle and muscle damage with exertion. It is unlike glycogen storage diseases resulting from known defects in glycogenolysis, glycolysis, and glycogen synthesis that have been described in humans and domestic animals. A genome-wide association identified GYS1, encoding skeletal muscle glycogen synthase (GS), as a candidate gene for PSSM. DNA sequence analysis revealed a mutation resulting in an arginine-to-histidine substitution in a highly conserved region of GS. Functional analysis demonstrated an elevated GS activity in PSSM horses, and haplotype analysis and allele age estimation demonstrated that this mutation is identical by descent among horse breeds. This is the first report of a gain-of-function mutation in GYS1 resulting in a glycogenosis. (c) 2008 Elsevier Inc. All rights reserved.