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

DSpace/Manakin Repository

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

Citable link to this page

 

 
Title: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients
Author: Guéant, Jean-Louis; Chéry, Céline; Oussalah, Abderrahim; Nadaf, Javad; Coelho, David; Josse, Thomas; Flayac, Justine; Robert, Aurélie; Koscinski, Isabelle; Gastin, Isabelle; Filhine-Tresarrieu, Pierre; Pupavac, Mihaela; Brebner, Alison; Watkins, David; Pastinen, Tomi; Montpetit, Alexandre; Hariri, Fadi; Tregouët, David; Raby, Benjamin A; Chung, Wendy K.; Morange, Pierre-Emmanuel; Froese, D. Sean; Baumgartner, Matthias R.; Benoist, Jean-François; Ficicioglu, Can; Marchand, Virginie; Motorin, Yuri; Bonnemains, Chrystèle; Feillet, François; Majewski, Jacek; Rosenblatt, David S.

Note: Order does not necessarily reflect citation order of authors.

Citation: Guéant, J., C. Chéry, A. Oussalah, J. Nadaf, D. Coelho, T. Josse, J. Flayac, et al. 2018. “A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients.” Nature Communications 9 (1): 67. doi:10.1038/s41467-017-02306-5. http://dx.doi.org/10.1038/s41467-017-02306-5.
Full Text & Related Files:
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.
Published Version: doi:10.1038/s41467-017-02306-5
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754367/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868867
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters