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

• Published in: Chinese medical journal Vol. 131; no. 4; pp. 448 - 453
• Main Authors: Liu, Hua-Xu, Pu, Chuan-Qiang, Shi, Qiang, Zhang, Yu-Tong, Ban, Rui
• Format: Journal Article
• Language: English
• Published: China Wolters Kluwer India Pvt. Ltd 20-02-2018; Medknow Publications and Media Pvt. Ltd; Lippincott Williams & Wilkins Ovid Technologies; School of Medicine, Nankai University, Tianjin 300071, China; Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China%Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Adenosine triphosphatase; Adolescent; Adult; Age; Alpha-glucosidase; DNA Mutational Analysis; Genetic Heterogeneity; Glycogen Storage Disease Type II; alpha-Glucosidases - genetics; Biopsy; Chinese (Asian people); Dehydrogenases; Deoxyribonucleic acid; DNA; Enzymes; Female; Gene mutation; Genes; Genetic aspects; Genetic testing; Genomes; Glycogen Storage Disease Type II - genetics; Glycogen Storage Disease Type II - pathology; Glycogen storage diseases; Health aspects; Humans; Kinases; Laboratories; Male; Mutation; Original; Patients; Software; Statistical analysis; Young Adult; 基因变化;疾病诊断;中国;肌肉纤维;鉴定;基因测试;可变性;遗传型; China; Singapore; United States > US; Germany; Taiwan; Glycogen Storage Disease Type II; DNA Mutational Analysis; Genetic Heterogeneity; Alpha-glucosidase; Glycogen Storage Disease Type
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.225056

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.