Zhang B L, Ye Z, Xu R L, You X H, Qin Y W, Wu H, Cao J, Zhang J L, Zheng X, Zhao X X
Department of Cardiovascular Diseases, Changhai Hospital, Second Military Medical University, Shanghai, China.
Clin Genet. 2014 Sep;86(3):287-91. doi: 10.1111/cge.12267. Epub 2013 Oct 25.
The Wolff-Parkinson-White (WPW) syndrome was believed to be associated with PRKAG2 gene mutations. In this study, we verified the pathopoiesis of G100S mutation, a novel mutation only discovered in Chinese patients with WPW, in cardiac disorder. Similar to R302Q, when overexpressed PRKAG2 G100S mutant in zebrafish, we observed a thicker heart wall, detected a decreased AMPK enzymatic activity by tissue AMPK kinase activity colorimetric technique, as well as examined an increased glycogen storage in heart wall using the method for periodic acid-Schiff staining, in comparison with the zebrafish without exogenous PRKAG2 (mock) or with wild-type PRKAG2 (WT). Taken together, we concluded PRKAG2 G100S mutation might contribute to impair the AMP-activated protein kinase function, which resulted in increased cardiac glycogen storage, serving as a pathogenesis for WPW syndrome in Chinese.
预激综合征（WPW）被认为与PRKAG2基因突变有关。在本研究中，我们验证了仅在中国WPW患者中发现的新型突变G100S在心脏疾病中的发病机制。与R302Q相似，当在斑马鱼中过表达PRKAG2 G100S突变体时，与未注射外源性PRKAG2（对照）或注射野生型PRKAG2（WT）的斑马鱼相比，我们观察到心脏壁增厚，通过组织AMPK激酶活性比色技术检测到AMPK酶活性降低，以及使用过碘酸希夫染色法检测到心脏壁中糖原储存增加。综上所述，我们得出结论，PRKAG2 G100S突变可能导致AMP激活的蛋白激酶功能受损，从而导致心脏糖原储存增加，这是中国WPW综合征的发病机制。
