Abstract
PMM2-CDG (MIM#212065) is the most common type of congenital disorders of glycosylation (CDG) caused by mutations in PMM2 (MIM#601785). In Estonia, five patients from three families have been diagnosed with PMM2-CDG. Our aim was to evaluate the presence of different PMM2-CDG-causing mutations in a population-based cohort and to calculate the expected frequency of PMM2-CDG in Estonia. Also, we analyzed the prevalence of PMM2-CDG based on our patient group data. To calculate the expected frequency of PMM2-CDG, we used the whole genome sequencing data of 2,244 participants from biobank of the Estonian Genome Center, University of Tartu. Nineteen individuals carried mutated PMM2 alleles and altogether, five different mutations were identified. The observed carrier frequency for all PMM2 disease-causing mutations was thus 1/118, and for the most frequent mutation p.R141H, 1/224. The expected frequency of the disease in Estonian population is 1/77,000. It is comparable to the current prevalence of PMM2-CDG for the less than 18 years age group, which is 1/79,000. In conclusion, the frequency of PMM2-CDG in Estonia is lower than in other European populations reported thus far. We demonstrate that biobank data can be useful for gaining new information about the epidemiology of the PMM2-CDG.
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Acknowledgements
This work was supported and funded by the Estonian Research Council grant PUT355, EU H2020 grant 692145, Estonian Research Council Grant IUT20-60, IUT24-6 and European Union through the European Regional Development Fund Project No. 2014-2020.4.01.15-0012 GENTRANSMED.
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Communicated by: Eva Morava, MD PhD
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The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Concise One-Sentence Take-Home Message
The expected frequency of the PMM2-CDG in Estonian population is 1/77,000.
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Details of the Contributions of Individual Authors
Mari-Anne Vals – performed serum transferrin isoelectric focusing to four patients, analyzed the population cohort data, performed statistical analysis, and compiled the manuscript.
Sander Pajusalu – analyzed the population cohort data, performed statistical analysis, coordinated analysis between different centers, and compiled the manuscript.
Mart Kals – analyzed biobank data, including quality control and compiled the manuscript.
Reedik Mägi – analyzed biobank data and compiled the manuscript.
Katrin Õunap – planned the study, diagnosed PMM2-CDG patients, coordinated work between different centers, and compiled the manuscript.
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Mari-Anne Vals.
A Competing Interest Statement
The authors Mari-Anne Vals, Sander Pajusalu, Mart Kals, Reedik Mägi, and Katrin Õunap declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
Details of Funding
This work was supported and funded by the Estonian Research Council grant PUT355, EU H2020 grant 692145, Estonian Research Council Grant IUT20-60, IUT24-6 and European Union through the European Regional Development Fund Project No. 2014-2020.4.01.15-0012 GENTRANSMED.
Details of Ethics Approval
This study was approved by the Research Ethics Committee of the University of Tartu (181/T-16, 20.04.2009 and 235/M-13, 17.03.2014). All participants in Estonian Biobank have signed a broad consent for using their data for research, and we also have an approval from the local ethics committee to use the omics data of gene donors of Estonian Biobank for genetic research (approval 234/T-12 for “Omics for health: an integrated approach to understand and predict human disease”).
A Patient Consent Statement
Informed consent was obtained from the parents of the five patients.
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Vals, MA., Pajusalu, S., Kals, M., Mägi, R., Õunap, K. (2017). The Prevalence of PMM2-CDG in Estonia Based on Population Carrier Frequencies and Diagnosed Patients. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 39. JIMD Reports, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_41
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DOI: https://doi.org/10.1007/8904_2017_41
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