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Abstract：
Glycogen storage disease XV is caused by variants in the glycogenin-1 gene, GYG1, and presents as a predominant skeletal myopathy or cardiomyopathy. We describe two patients with late-onset myopathy and biallelic GYG1 variants. In patient 1, the novel c.144-2A>G splice acceptor variant and the novel frameshift variant c.631delG (p.Val211Cysfs*30) were identified, and in patient 2, the previously described c.304G>C (p.Asp102His) and c.487delG (p.Asp163Thrfs*5) variants were found. Protein analysis showed total absence of glycogenin-1 expression in patient 1, whereas in patient 2 there was reduced expression of glycogenin-1, with the residual protein being non-functional. Both patients showed glycogen and polyglucosan storage in their muscle fibers, as revealed by PAS staining and electron microscopy. Age at onset of the myopathy phenotype was 53 years and 70 years respectively, with the selective pattern of muscle involvement on MRI corroborating the pattern of weakness. Cardiac evaluation of patient 1 and 2 did not show any specific abnormalities linked to the glycogenin-1 deficiency. In patient 2, who was shown to express the p.Asp102His mutated glycogenin-1, cardiac evaluation was still normal at age 77 years. This contrasts with the association of the p.Asp102His variant in homozygosity with a severe cardiomyopathy in several cases with an onset age between 30 and 50 years. This finding might indicate that the level of p.Asp102His mutated glycogenin-1 determines if a patient will develop a cardiomyopathy.
摘要：
糖原贮积病XV是由糖原蛋白-1基因的变异体引起的，GYG1，并表现为主要的骨骼肌病或心肌病。我们描述了两名患有迟发性肌病和双等位基因GYG1变异的患者。在患者1中，新型c.144-2A>G剪接受体变体和新型移码变体c.631delG（p。Val211Cysfs*30）被鉴定，并且在患者2中，先前描述的c.304G>C（p。Asp102His）和c.487delG（p。发现了Asp163Thrfs*5）变体。蛋白质分析显示,在患者1中完全不存在糖原蛋白-1表达,而在患者2中,糖原蛋白-1的表达降低,残余蛋白质无功能。两名患者都显示糖原和聚葡聚糖在他们的肌纤维中储存，PAS染色和电子显微镜显示。肌病表型的发病年龄分别为53岁和70岁,MRI上肌肉受累的选择性模式证实了无力的模式。患者1和2的心脏评估未显示与糖原-1缺乏相关的任何特定异常。在显示表达p.Asp102His突变的糖原-1的患者2中，心脏评估在77岁时仍然正常。这与纯合性p.Asp102His变体与严重心肌病的关联形成对比，在一些发病年龄在30至50岁之间的病例中。这一发现可能表明p.Asp102His突变的糖原蛋白-1的水平决定了患者是否会发展为心肌病。
