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The Prevalence of PMM2-CDG in Estonia Based on Population Carrier Frequencies and Diagnosed Patients

  • Mari-Anne Vals
  • Sander Pajusalu
  • Mart Kals
  • Reedik Mägi
  • Katrin Õunap
Research Report
Part of the JIMD Reports book series (JIMD, volume 39)

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.

Keywords

Biobank Carrier frequency N-glycosylation p.R141H PMM2-CDG 

Notes

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.

References

  1. Bjursell C, Erlandson A, Nordling M et al (2000) PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families. Hum Mutat 16:395–400CrossRefPubMedGoogle Scholar
  2. Kjaergaard S, Skovby F, Schwartz M (1998) Absence of homozygosity for predominant mutations in PMM2 in Danish patients with carbohydrate-deficient glycoprotein syndrome type 1. Eur J Hum Genet 6:331–336CrossRefPubMedGoogle Scholar
  3. Leitsalu L, Haller T, Esko T et al (2015) Cohort profile: Estonian biobank of the Estonian Genome Center, University of Tartu. Int J Epidemiol 44:1137–1147CrossRefPubMedGoogle Scholar
  4. Martinsson T, Bjursell C, Stibler H et al (1994) Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p, and linkage disequilibrium to microsatellite marker D16S406. Hum Mol Genet 3:2037–2042PubMedGoogle Scholar
  5. Matthijs G, Schollen E, Van Schaftingen E, Cassiman JJ, Jaeken J (1998) Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. Am J Hum Genet 62:542–550CrossRefPubMedPubMedCentralGoogle Scholar
  6. Matthijs G, Schollen E, Bjursell C et al (2000) Mutations in PMM2 that cause congenital disorders of glycosylation, type Ia (CDG-Ia). Hum Mutat 16:386–394CrossRefPubMedGoogle Scholar
  7. Najmabadi H, Hu H, Garshasbi M et al (2011) Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478:57–63CrossRefPubMedGoogle Scholar
  8. Neumann LM, von Moers A, Kunze J, Blankenstein O, Marquardt T (2003) Congenital disorder of glycosylation type 1a in a macrosomic 16-month-old boy with an atypical phenotype and homozygosity of the N216I mutation. Eur J Pediatr 162:710–713CrossRefPubMedGoogle Scholar
  9. Perez B, Briones P, Quelhas D et al (2011) The molecular landscape of phosphomannose mutase deficiency in iberian peninsula: identification of 15 population-specific mutations. JIMD Rep 1:117–123CrossRefPubMedPubMedCentralGoogle Scholar
  10. R Core Team (2016) R: a language and environment for statistical computing. In: Book R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  11. Schollen E, Kjaergaard S, Legius E, Schwartz M, Matthijs G (2000) Lack of Hardy-Weinberg equilibrium for the most prevalent PMM2 mutation in CDG-Ia (congenital disorders of glycosylation type Ia). Eur J Hum Genet 8:367–371CrossRefPubMedGoogle Scholar
  12. Stenson PD, Mort M, Ball EV et al (2009) The human gene mutation database: 2008 update. Genome Med 1:13CrossRefPubMedPubMedCentralGoogle Scholar
  13. Vals MA, Morava E, Teeaar K et al (2017) Three families with mild PMM2-CDG and normal cognitive development. Am J Med Genet A 173:1620–1624CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Mari-Anne Vals
    • 1
    • 2
    • 3
  • Sander Pajusalu
    • 1
    • 2
  • Mart Kals
    • 4
  • Reedik Mägi
    • 4
  • Katrin Õunap
    • 1
    • 2
  1. 1.Department of Clinical Genetics, United LaboratoriesTartu University HospitalTartuEstonia
  2. 2.Department of Clinical GeneticsInstitute of Clinical Medicine, University of TartuTartuEstonia
  3. 3.Children’s ClinicTartu University HospitalTartuEstonia
  4. 4.Estonian Genome CenterUniversity of TartuTartuEstonia

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