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RFT1-CDG: Absence of Epilepsy and Deafness in Two Patients with Novel Pathogenic Variants

  • D. QuelhasEmail author
  • J. Jaeken
  • A. Fortuna
  • L. Azevedo
  • A. Bandeira
  • G. Matthijs
  • E. Martins
Research Report
Part of the JIMD Reports book series (JIMD, volume 43)

Abstract

This report is on two novel patients with RFT1-CDG. Their phenotype is characterized by mild psychomotor disability, behavioral problems, ataxia, and mild dysmorphism. Neither of them shows signs of epilepsy, which was observed in all RFT1-CDG patients reported to date (n = 14). Also, deafness, which is often associated with this condition, was not observed in our patients. Molecular analysis of RFT1 showed biallelic missense variants including three novel ones: c.827G > A (p.G276D), c.73C > T (p.R25W), and c.208T > C (p.C70R).

Keywords

CDG Congenital disorder(s) of glycosylation Deafness Phenotype RFT1 

Notes

Acknowledgments

The authors thank Prof. T. Hennet for the lipid-linked oligosaccharide analysis of fibroblasts from both patients.

References

  1. Aeby A, Prigogine C, Vilain C et al (2016) RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy. Epileptic Disord 18:92–96PubMedGoogle Scholar
  2. Barba C, Darra F, Cusmai R et al (2016) Congenital disorders of glycosylation presenting as epileptic encephalopathy with migrating partial seizures in infancy. Dev Med Child Neurol 58:1085–1091CrossRefGoogle Scholar
  3. Bastaki F, Bizzari S, Hamici S et al (2018) Single-center experience of N-linked congenital disorders of glycosylation with a summary of molecularly characterized cases in Arabs. Ann Hum Genet 82(1):35–47CrossRefGoogle Scholar
  4. Clayton PT, Grunewald S (2009) Comprehensive description of the phenotype of the first case of congenital disorder of glycosylation due to RFT1 deficiency (CDG In). J Inherit Metab Dis 32(Suppl 1):S137–S139CrossRefGoogle Scholar
  5. Haeuptle MA, Hennet T (2009) Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Hum Mutat 30:1628–1641CrossRefGoogle Scholar
  6. Haeuptle MA, Pujol FM, Neupert C et al (2008) Human RFT1 deficiency leads to a disorder of N-linked glycosylation. Am J Hum Genet 82:600–606CrossRefGoogle Scholar
  7. Imtiaz F, Worthington V, Champion M et al (2000) Genotypes and phenotypes of patients in the UK with carbohydrate-deficient glycoprotein syndrome type 1. J Inherit Metab Dis 23:162–174CrossRefGoogle Scholar
  8. Jaeken J, Vleugels W, Régal L et al (2009) RFT1-CDG: deafness as a novel feature of congenital disorders of glycosylation. J Inherit Metab Dis 32(Suppl 1):S335–S338CrossRefGoogle Scholar
  9. Monies D, Abouelhoda M, AlSayed M et al (2017) The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes. Hum Genet 136:921–939CrossRefGoogle Scholar
  10. Ondruskova N, Vesela K, Hansikova H, Magner M, Zeman J, Honzik T (2012) RFT1-CDG in adult siblings with novel mutations. Mol Genet Metab 107:760–762CrossRefGoogle Scholar
  11. Pérez-Cerdá C, Girós ML, Serrano M et al (2017) A population-based study on congenital disorders of protein N- and combined with O-glycosylation experience in clinical and genetic diagnosis. J Pediatr 183:170–177CrossRefGoogle Scholar
  12. Vleugels W, Haeuptle MA, Ng BG et al (2009) RFT1 deficiency in three novel CDG patients. Hum Mutat 30:1428–1434CrossRefGoogle Scholar
  13. Vleugels W, Duvet S, Peanne R et al (2011) Identification of phosphorylated oligosaccharides in cells of patients with a congenital disorders of glycosylation (CDG-I). Biochimie 93:823–833CrossRefGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • D. Quelhas
    • 1
    • 2
    Email author
  • J. Jaeken
    • 3
  • A. Fortuna
    • 1
    • 2
  • L. Azevedo
    • 4
    • 5
    • 6
  • A. Bandeira
    • 7
  • G. Matthijs
    • 8
  • E. Martins
    • 2
    • 7
  1. 1.Unidade de Bioquímica Genética, Centro de Genética Médica, Centro Hospitalar do PortoPortoPortugal
  2. 2.Unit for Multidisciplinary Research in Biomedicine, ICBAS, UPPortoPortugal
  3. 3.Center for Metabolic DiseasesKU LeuvenLeuvenBelgium
  4. 4.i3S-Instituto de Investigação e Inovação em Saúde, UP, Population Genetics and Evolution GroupPortoPortugal
  5. 5.IPATIMUP-Institute of Molecular Pathology and Immunology, UPPortoPortugal
  6. 6.FCUP-Department of Biology, Faculty of Sciences, UPPortoPortugal
  7. 7.Centro Referência Doenças Hereditárias do Metabolismo, Centro Hospitalar do PortoPortoPortugal
  8. 8.Department of Human GeneticsKU LeuvenLeuvenBelgium

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