Abstract
Glycogen storage disease type III (GSD III), a rare autosomal recessive disease characterized by hepatomegaly, fasting hypoglycemia, growth retardation, progressive myopathy and cardiomyopathy, is caused by deficiency of the glycogen debranching enzyme (AGL). Direct sequencing of human AGL cDNA and genomic DNA has enabled analysis of the underlying genetic defects responsible for GSD III. To date, the frequent mutations in different areas and populations have been described in Italy, Japan, Faroe Islands and Mediterranean area, whereas little has been performed in Chinese population. Here we report a sequencing-based mutation analysis in 43 Chinese patients with GSD III from 41 families. We identified 51 different mutations, including 15 splice-site (29.4%), 11 small deletions (21.6%), 12 nonsense (23.5%), 7 missense (13.7%), 5 duplication (9.8%) and 1 complex deletion/insertion (2.0%), 31 of which are novel mutations. The most common mutation is c.1735+1G>T (11.5%). The association of AGL missense and small in-frame deletion mutations with normal creatine kinase level was observed. Our study extends the spectrum of AGL mutations and suggests a genotype–phenotype correlation in GSD III.
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Acknowledgements
We thank all patients and their family members who participated in this study. This work was funded by the National 863 Program of China (2007AA02Z440), the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period (2012BAI09B00), the National Natural Science Foundation of China (81241032 and 30871355), the Public Science and Technology Research Funds Projects of Health (201302001), and the Presidential Foundation of Chinese Academy of Medical Sciences & Peking Union Medical College.
Author contributions
ZQ, MS and XZ conceived and designed the study. CL carried out the experiments and analyzed the gene mutation results. WM, ZQ and WW performed the study of the clinical part. CL, ZQ, MS and XZ wrote the manuscript. All authors revised and approved the final manuscript.
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Lu, C., Qiu, Z., Sun, M. et al. Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations. J Hum Genet 61, 641–645 (2016). https://doi.org/10.1038/jhg.2016.24
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DOI: https://doi.org/10.1038/jhg.2016.24
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