Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia.
Perron Institute for Neurological and Translational Science and The University of Western Australia, Perth 6009, Western Australia, Australia.
Genes (Basel). 2020 Jan 28;11(2):135. doi: 10.3390/genes11020135.
Pompe disease, or glycogen storage disease II is a rare, progressive disease leading to skeletal muscle weakness due to deficiency of the acid α-1,4-glucosidase enzyme (GAA). The severity of disease and observed time of onset is subject to the various combinations of heterozygous alleles. Here we have characterized two novel mutations: c.2074C>T and c.1910_1918del, and a previously reported c.1082C>G mutation of uncertain clinical significance. These mutations were found in three unrelated patients with adult-onset Pompe disease carrying the common c.-32-13T>G mutation. The c.2074 C>T nonsense mutation has obvious consequences on expression but the c.1910_1918del (deletion of 3 amino acids) and c.1082C>G missense variants are more subtle DNA changes with catastrophic consequences on GAA activity. Molecular and clinical analyses from the three patients corresponded with the anticipated pathogenicity of each mutation.
庞贝病，又称糖原贮积症 II 型，是一种罕见的进行性疾病，由于酸性α-1,4-葡萄糖苷酶（GAA）酶的缺乏，导致骨骼肌无力。疾病的严重程度和发病时间观察到的情况取决于杂合等位基因的各种组合。在这里，我们描述了两种新的突变：c.2074C>T 和 c.1910_1918del，以及之前报道的具有不确定临床意义的 c.1082C>G 突变。这些突变存在于 3 位携带常见 c.-32-13T>G 突变的成年起病庞贝病患者中。c.2074C>T 无义突变对表达有明显影响，但 c.1910_1918del（3 个氨基酸缺失）和 c.1082C>G 错义变体是更细微的 DNA 变化，对 GAA 活性有灾难性的影响。来自这 3 位患者的分子和临床分析与每个突变的预期致病性相对应。
