Abstract
Glycogen storage disease type III (GSD III) is an autosomal recessive disorder that is characterized by the excessive accumulation of abnormal glycogen in the liver and muscles and is caused by a deficiency in glycogen debranching enzyme (amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL)) activity. To investigate the molecular characteristics of GSD III patients in Korea, we have sequenced the AGL gene in eight children with GSD III. All patients were compound heterozygotes. We identified 10 different mutations (five novel and five previously reported). The novel mutations include one nonsense (c.1461G>A, p.W487X), three splicing (c.293+4_293+6delAGT in IVS4, c.460+1G>T in IVS5, c.2682-8A>G in IVS21) and one missense mutation (c.2591G>C, p.R864P). Together, p.R285X, c.1735+1G>T and p.L1139P accounted for 56% of all alleles, while the remaining mutations are heterogeneous. These three mutations can be common in Korea, and further larger studies are needed to confirm our findings.
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References
Coleman, R. A., Winter, H. S., Wolf, B., Gilchrist, J. M. & Chen, Y. T. Glycogen storage disease type III (glycogen debranching enzyme deficiency): correlation of biochemical defects with myopathy and cardiomyopathy. Ann. Intern. Med. 116, 896–900 (1992).
Shen, J., Bao, Y., Liu, H. M., Lee, P., Leonard, J. V. & Chen, Y. T. Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle. J. Clin. Invest. 98, 352–357 (1996).
Bao, Y., Dawson, T. L. Jr. & Chen, Y. T. Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5′ flanking region. Genomics 38, 155–165 (1996).
Kishnani, P. S., Austin, S. L., Arn, P., Bali, D. S., Boney, A., Case, L. E. et al. Glycogen storage disease type III diagnosis and management guidelines. Genet. Med. 12, 446–463 (2010).
Parvari, R., Moses, S., Shen, J., Hershkovitz, E., Lerner, A. & Chen, Y. T. A single-base deletion in the 3′-coding region of glycogen-debranching enzyme is prevalent in glycogen storage disease type IIIA in a population of North African Jewish patients. Eur. J. Hum. Genet. 5, 266–270 (1997).
Mili, A., Ben Charfeddine, I., Mamai, O., Abdelhak, S., Adala, L., Amara, A. et al. Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III. J. Hum. Genet. 57, 170–175 (2012).
Aoyama, Y., Ozer, I., Demirkol, M., Ebara, T., Murase, T., Podskarbi, T. et al. Molecular features of 23 patients with glycogen storage disease type III in Turkey: a novel mutation p.R1147G associated with isolated glucosidase deficiency, along with 9 AGL mutations. J. Hum. Genet. 54, 681–686 (2009).
Santer, R., Kinner, M., Steuerwald, U., Kjaergaard, S., Skovby, F., Simonsen, H. et al. Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands. Eur. J. Hum. Genet. 9, 388–391 (2001).
Lam, C. W., Lee, A. T., Lam, Y. Y., Wong, T. W., Mak, T. W., Fung, W. C. et al. DNA-based subtyping of glycogen storage disease type III: mutation and haplotype analysis of the AGL gene in Chinese. Mol. Genet. Metab. 83, 271–275 (2004).
Oh, S. H., Park, H. D., Ki, C. S., Choe, Y. H. & Lee, S. Y. Biochemical and molecular investigation of two Korean patients with glycogen storage disease type III. Clin. Chem. Lab. Med. 46, 1245–1249 (2008).
Ko, J. M., Kim, G. H. & Yoo, H. W. AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III. J. Genet. Med. 4, 72–79 (2007).
Goldstein, J. L., Austin, S. L., Boyette, K., Kanaly, A., Veerapandiyan, A., Rehder, C. et al. Molecular analysis of the AGL gene: identification of 25 novel mutations and evidence of genetic heterogeneity in patients with Glycogen Storage Disease Type III. Genet. Med. 12, 424–430 (2010).
Okubo, M., Horinishi, A., Takeuchi, M., Suzuki, Y., Sakura, N., Hasegawa, Y. et al. Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan. Hum. Genet. 106, 108–115 (2000).
Endo, Y., Horinishi, A., Vorgerd, M., Aoyama, Y., Ebara, T., Murase, T. et al. Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey. J. Hum. Genet. 51, 958–963 (2006).
Lucchiari, S., Pagliarani, S., Salani, S., Filocamo, M., Di Rocco, M., Melis, D. et al. Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL. Hum. Mutat. 27, 600–601 (2006).
Shen, J. J. & Chen, Y. T. Molecular characterization of glycogen storage disease type III. Curr. Mol. Med. 2, 167–175 (2002).
Horinishi, A., Okubo, M., Tang, N. L., Hui, J., To, K. F., Mabuchi, T. et al. Mutational and haplotype analysis of AGL in patients with glycogen storage disease type III. J. Hum. Genet. 47, 55–59 (2002).
Endo, Y., Fateen, E., Aoyama, Y., Horinishi, A., Ebara, T., Murase, T. et al. Molecular characterization of Egyptian patients with glycogen storage disease type IIIa. J. Hum. Genet. 50, 538–542 (2005).
Crushell, E., Treacy, E. P., Dawe, J., Durkie, M. & Beauchamp, N. J. Glycogen storage disease type III in the Irish population. J. Inherit. Metab. Dis. 3, 215–218 (2010).
Okubo, M., Aoyama, Y. & Murase, T. A novel donor splice site mutation in the glycogen debranching enzyme gene is associated with glycogen storage disease type III. Biochem. Biophys. Res. Commun. 225, 695 (1996).
Ogimoto, A., Okubo, M., Okayama, H., Shin, Y. S., Endo, Y., Ebara, T. et al. A Japanese patient with cardiomyopathy caused by a novel mutation R285X in the AGL gene. Circ. J. 71, 1653–1656 (2007).
Lucchiari, S., Donati, M. A., Parini, R., Melis, D., Gatti, R., Bresolin, N. et al. Molecular characterisation of GSD III subjects and identification of six novel mutations in AGL. Hum. Mutat. 20, 480 (2002).
Shaiu, W. L., Kishnani, P. S., Shen, J., Liu, H. M. & Chen, Y. T. Genotype-phenotype correlation in two frequent mutations and mutation update in type III glycogen storage disease. Mol. Genet. Metab. 69, 16–23 (2000).
Lucchiari, S., Fogh, I., Prelle, A., Parini, R., Bresolin, N., Melis, D. et al. Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean area. Am. J. Med. Genet. 109, 183–190 (2002).
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This study was supported by Grant no. 0420120490 from the SNUH Research Fund.
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Ko, J., Moon, J., Seo, J. et al. A mutation analysis of the AGL gene in Korean patients with glycogen storage disease type III. J Hum Genet 59, 42–45 (2014). https://doi.org/10.1038/jhg.2013.117
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DOI: https://doi.org/10.1038/jhg.2013.117
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