IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-017-02306-5.html
   My bibliography  Save this article

A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

Author

Listed:
  • Jean-Louis Guéant

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Céline Chéry

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Abderrahim Oussalah

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Javad Nadaf

    (McGill University and Research Institute McGill University Health Centre)

  • David Coelho

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Thomas Josse

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Justine Flayac

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Aurélie Robert

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Isabelle Koscinski

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Isabelle Gastin

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Pierre Filhine-Tresarrieu

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Mihaela Pupavac

    (McGill University and Research Institute McGill University Health Centre)

  • Alison Brebner

    (McGill University and Research Institute McGill University Health Centre)

  • David Watkins

    (McGill University and Research Institute McGill University Health Centre)

  • Tomi Pastinen

    (McGill University and Research Institute McGill University Health Centre)

  • Alexandre Montpetit

    (McGill University and Research Institute McGill University Health Centre)

  • Fadi Hariri

    (McGill University and Research Institute McGill University Health Centre)

  • David Tregouët

    (Team Genomics & Pathophysiology of Cardiovascular Diseases)

  • Benjamin A Raby

    (Harvard Medical School)

  • Wendy K. Chung

    (Columbia University)

  • Pierre-Emmanuel Morange

    (INSERM, UMR_S1062, Nutrition Obesity and Risk of Thrombosis, Aix-Marseille University)

  • D. Sean Froese

    (University Children’s Hospital)

  • Matthias R. Baumgartner

    (University Children’s Hospital)

  • Jean-François Benoist

    (Hôpital Robert Debré)

  • Can Ficicioglu

    (Perelman School of Medicine at the University of Pennsylvania)

  • Virginie Marchand

    (UMR7365 CNRS - Université de Lorraine and FR3209 CNRS- Université de Lorraine)

  • Yuri Motorin

    (UMR7365 CNRS - Université de Lorraine and FR3209 CNRS- Université de Lorraine)

  • Chrystèle Bonnemains

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • François Feillet

    (University of Lorraine and University Hospital Centre of Nancy (CHRU Nancy))

  • Jacek Majewski

    (McGill University and Research Institute McGill University Health Centre)

  • David S. Rosenblatt

    (McGill University and Research Institute McGill University Health Centre)

Abstract

To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name “epi-cblC”. The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. MMACHC is flanked by CCDC163P and PRDX1, which are in the opposite orientation. The epimutation is present in three generations and results from PRDX1 mutations that force antisense transcription of MMACHC thereby possibly generating a H3K36me3 mark. The silencing of PRDX1 transcription leads to partial hypomethylation of the epiallele and restores the expression of MMACHC. This example of epi-cblC demonstrates the need to search for compound epigenetic-genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios.

Suggested Citation

  • Jean-Louis Guéant & Céline Chéry & Abderrahim Oussalah & Javad Nadaf & David Coelho & Thomas Josse & Justine Flayac & Aurélie Robert & Isabelle Koscinski & Isabelle Gastin & Pierre Filhine-Tresarrieu , 2018. "A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02306-5
    DOI: 10.1038/s41467-017-02306-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-02306-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-02306-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02306-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.