Gene ( IF 3.5 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.gene.2021.145967 Cinthia Amiñoso 1 , Jesús Solera 2
Glycogenosis type II (GSDII), or Pompe disease (MIM 232300), is an inherited autosomal recessive disorder caused by deficiency of the lysosomal acid-α-glucosidase. Mutations in the GAA gene alter normal enzyme production and lead to progressive buildup of intralysosomal glycogen, which plays an essential role in the severity and progression of the disease. We report here the study of 76 patients from Spain with either infantile or late onset form of Pompe disease. The analysis consisted in the molecular study of exons and intron flanking fragments of GAA gene. We have identified 55 different molecular pathogenic variants, 12 of them not previously described. In addition, we have determined a frequency of 84.37% for the c.-32-13T>G mutation in patients with the late-onset form of the disease. Functional characterization of some splice mutations showed deleterious mechanisms on the processing of mRNA.
中文翻译:
76 名西班牙庞贝病患者的遗传分析:12 种新型致病性 GAA 变异的鉴定和剪接变异的功能表征
II 型糖原病 (GSDII) 或庞贝病 (MIM 232300) 是一种由溶酶体酸-α-葡萄糖苷酶缺乏引起的遗传性常染色体隐性遗传病。GAA基因的突变会改变正常的酶产生并导致溶酶体内糖原的逐渐积累,这在疾病的严重程度和进展中起着至关重要的作用。我们在此报告对来自西班牙的 76 名患有婴儿型或晚发型庞贝病的患者的研究。分析包括对GAA的外显子和内含子侧翼片段的分子研究基因。我们已经确定了 55 种不同的分子致病变异,其中 12 种以前没有描述过。此外,我们已经确定了晚发型患者中 c.-32-13T>G 突变的频率为 84.37%。一些剪接突变的功能表征显示出对 mRNA 加工的有害机制。