Abstract
Glycogen-storage disease type II (GSDII) is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA). The residual GAA activity is largely related to the severity of the clinical course. Most patients with infantile-onset GSDII do not show any enzyme activity, whereas patients with the late-onset forms of GSDII show various degrees of GAA activity. We performed a molecular genetic study on a Japanese boy with childhood-onset GSDII. The patient was a compound heterozygote for a newly discovered splice-site c.546G>T mutation and a recurrent missense p.R600C mutation, which usually causes the fatal infantile form in a homozygous state. The c.546G>T mutation, which did not alter the amino-acid sequence, was positioned at the last base of exon 2. cDNA-sequencing analysis revealed that c.546G>T was a leaky splice mutation, leading to the production of a normally spliced transcript, which was responsible for the low-level (approximately 10%) expression of the active enzyme in the patient's fibroblasts.
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Acknowledgements
We sincerely thank the members of the family for their participation, Dr Ikuya Nonaka and Dr Ichizo Nishino for their pathological examination of the muscle and Dr Hideo Sugie for his enzyme assay. This work was supported by a grant from Takeda Science Foundation for MM.
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Maimaiti, M., Takahashi, S., Okajima, K. et al. Silent exonic mutation in the acid-α-glycosidase gene that causes glycogen storage disease type II by affecting mRNA splicing. J Hum Genet 54, 493–496 (2009). https://doi.org/10.1038/jhg.2009.66
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DOI: https://doi.org/10.1038/jhg.2009.66
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