Intron retention is among six unreported AGL mutations identified in Malaysian GSD III patients
Document Type
Article
Publication Date
1-1-2019
Abstract
Background: Glycogen storage disease type III is an autosomal recessive disorder that is caused by deficiencies of the glycogen debranching enzyme. Mutations within the AGL gene have been found to be heterogeneous, with some common mutations being reported in certain populations. The mutation spectrum of AGL gene in the multi-ethnic Malaysian population is still unknown. Objective: The present study seeks to determine the mutation spectrum of the AGL gene in Malaysian population. Methods: A total of eleven patients (eight Malay, two Chinese and one Bajau) were investigated. Genomic DNA was extracted and subsequently the AGL gene was amplified using specific primers and sequenced. Mutations found were screened in 150 healthy control samples either by restriction enzyme digestion assay or TaqMan® SNP Genotyping assay. Results: We identified six unreported mutations (c.1423+1G>T, c.2914_2915delAA, c.3814_3815delAG, c.4333T>G, c.4490G>A, c.4531_4534delTGTC) along with three previously reported mutations (c.99C>T, c.1783C>T, c.2681+1G>A). One of the six unreported mutation causes abnormal splicing and results in retention of intron 12 of the mature transcript, while another is a termination read-through. One of the reported mutation c.2681+1G>A was recurrently found in the Malay patients (n = 7 alleles; 31.8%). Conclusion: The mutation spectrum of the AGL gene in Malaysian patients has shown considerable heterogeneity, and all unreported mutations were absent in all 150 healthy control samples tested. © 2019, The Genetics Society of Korea.
Keywords
Catalytic domain, Glycogen debranching enzyme, Glycogen storage disease type III, Mutant proteins, Mutation
Divisions
fac_med
Funders
Ministry of Science, Technology and Innovation of Malaysia for the eScience fund (SF012-2012),University of Malaya for the UM Biotechnology and Bioproduct Research Cluster fund (RG071-12BIO)
Publication Title
Genes & Genomics
Volume
41
Issue
8
Publisher
Springer Verlag (Germany)