A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients
| العنوان: | A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients |
|---|---|
| المؤلفون: | 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. |
| المساهمون: | GONNET, JULIE, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), McGill University = Université McGill [Montréal, Canada], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Harvard Medical School [Boston] (HMS), University of Missouri [Columbia] (Mizzou), University of Missouri System, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), University hospital of Zurich [Zurich], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Perelman School of Medicine, University of Pennsylvania, Children’s Hospital of Philadelphia (CHOP ), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), McGill University, Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], University of Missouri [Columbia], Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), University of Pennsylvania [Philadelphia], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-15-IDEX-04-LUE,LUE,Lorraine Université d'Excellence(2016), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications Nature Communications, 2018, 9 (1), pp.67. ⟨10.1038/s41467-017-02306-5⟩ Nature Communications, Nature Publishing Group, 2018, 9 (1), pp.67. ⟨10.1038/s41467-017-02306-5⟩ |
| بيانات النشر: | Nature Portfolio, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | MESH: Mutation, MESH: Metabolism, Inborn Errors, MESH: Pedigree, Science, MESH: Azacitidine, MESH: Peroxiredoxins, MESH: Carrier Proteins, MESH: Base Sequence, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Article, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Epistasis, Genetic, lcsh:Science, MESH: Heterozygote, MESH: Humans, MESH: Alleles, nutritional and metabolic diseases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Male, MESH: Vitamin B 12, MESH: Enzyme Inhibitors, MESH: Fibroblasts, MESH: Family Health, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, MESH: Whole Genome Sequencing, MESH: Female |
| الوصف: | 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. Inborn errors of vitamin B12 metabolism of the cblC class are caused by mutations in the MMACHC gene. Here, Guéant et al. report epi-cblC, a class of cblC in which patients are compound heterozygous for a genetic mutation and a secondary epimutation at the MMACHC locus. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::0754f21f129d67519bccad352a828279Test https://doaj.org/article/cbd6be2fd8e245cb84a21aa02a029651Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....0754f21f129d67519bccad352a828279 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
|---|