Ili Syazwana Abdullah1, Ser-Huy Teh1, Fiqri Dizar Khaidizar2, Lock-Hock Ngu3, Wee-Teik Keng3, Sufin Yap4,5, Zulqarnain Mohamed6,7. 1. Genetics and Molecular Biology Unit, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia. 2. Centre for Research in Biotechnology for Agriculture, University of Malaya, 50603, Kuala Lumpur, Malaysia. 3. Genetics Department, Kuala Lumpur Hospital, 50586, Kuala Lumpur, Malaysia. 4. Division of Inherited Metabolic Disorders, Department of Paediatrics, University Malaya Medical Centre and Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. 5. Department of Inherited Metabolic Diseases, Sheffield Children's Hospital, NHS Foundation Trust, Western Bank, S10 2TH, Sheffield, UK. 6. Genetics and Molecular Biology Unit, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia. zulq@um.edu.my. 7. Institute of Advanced Studies, University of Malaya, 50603, Kuala Lumpur, Malaysia. zulq@um.edu.my.
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.
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.
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