Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease

作     者：Hua-Xu Liu Chuan-Qiang Pu Qiang Shi Yu-Tong Zhang Rui Ban Liu Hua-Xu;Pu Chuan-Qiang;Shi Qiang;Zhang Yu-Tong;Ban Rui

作者机构：Department of Neurology Chinese People's Liberation Army General Hospital Beijing 100853 China School of Medicine Nankai University Tianjin 300071 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2018年第131卷第4期

页      面：448-453页

核心收录：

学科分类：0710[理学-生物学] 090603[农学-临床兽医学] 1002[医学-临床医学] 07[理学] 09[农学] 0906[农学-兽医学] 071007[理学-遗传学] 

基　　金：This work was supported by grants of National Natural Science Foundation of China （No. 81501083 and 81671236）. 

主　　题：Alpha-glucosidase DNA Mutational Analysis Genetic Heterogeneity Glycogen Storage Disease Type Ⅱ 

摘      要：Background： Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene （GAA）. A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease （LOPD） who carried novel GAA gene mutations. Methods： Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. Results： Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones （c.796C〉A, c. 1057C〉T, c. 1201C〉A, c. 1780C〉T, c. 1799G〉C, c.2051C〉A, c.2235dupG）, were identified by genetic tests. Conclusions： The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.