Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature.
Accelerated aging
Chromatin remodeling
DNA methylation
Episignature
HIST1H1E
Intellectual disability
Rahman syndrome
Replicative senescence
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
07 01 2020
07 01 2020
Historique:
received:
11
09
2019
accepted:
26
12
2019
entrez:
9
1
2020
pubmed:
9
1
2020
medline:
17
8
2021
Statut:
epublish
Résumé
We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis.
Sections du résumé
BACKGROUND
We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern.
RESULTS
Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject.
CONCLUSIONS
We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis.
Identifiants
pubmed: 31910894
doi: 10.1186/s13148-019-0804-0
pii: 10.1186/s13148-019-0804-0
pmc: PMC6947958
doi:
Substances chimiques
H1-4 protein, human
0
Histones
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7Références
Epigenetics. 2017;12(11):923-933
pubmed: 28933623
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Am J Hum Genet. 2017 May 4;100(5):773-788
pubmed: 28475860
Am J Hum Genet. 2016 Oct 6;99(4):802-816
pubmed: 27616483
PLoS One. 2013 Jun 27;8(6):e67378
pubmed: 23826282
Epigenomics. 2019 Apr;11(5):563-575
pubmed: 30875234
Genome Biol. 2018 Jan 9;19(1):2
pubmed: 29310692
Am J Hum Genet. 2010 Feb 12;86(2):113-25
pubmed: 20060087
Cell Rep. 2013 Jun 27;3(6):2142-54
pubmed: 23746450
Pain. 2016 Jun;157(6):1314-24
pubmed: 26859820
Biochim Biophys Acta. 2013 Oct;1832(10):1673-96
pubmed: 23707412
J Hum Genet. 2017 Jun;62(6):589-597
pubmed: 28228639
Nat Commun. 2018 Jun 19;9(1):2397
pubmed: 29921915
Nat Commun. 2017 Aug 18;8(1):283
pubmed: 28819201
Epigenetics Chromatin. 2017 Mar 10;10:10
pubmed: 28293299
Genome Res. 2015 Oct;25(10):1473-81
pubmed: 26430157
BMC Bioinformatics. 2012 May 08;13:86
pubmed: 22568884
Cell. 2005 Dec 29;123(7):1199-212
pubmed: 16377562
Am J Hum Genet. 2018 Jan 4;102(1):156-174
pubmed: 29304373
Eur J Med Genet. 2014 May-Jun;57(6):293-7
pubmed: 24704790
Epigenetics Chromatin. 2015 Jan 27;8:6
pubmed: 25972926
Nat Commun. 2018 Nov 20;9(1):4885
pubmed: 30459321
Nat Rev Genet. 2013 May;14(5):347-59
pubmed: 23568486
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Clin Epigenetics. 2019 Apr 27;11(1):64
pubmed: 31029150
J Mol Diagn. 2016 Nov;18(6):834-841
pubmed: 27585064
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
EMBO Rep. 2015 Nov;16(11):1439-53
pubmed: 26474902
PLoS One. 2018 Dec 20;13(12):e0208915
pubmed: 30571772
Mol Brain. 2017 Sep 4;10(1):43
pubmed: 28870203
Am J Hum Genet. 2019 Sep 5;105(3):493-508
pubmed: 31447100
Transl Psychiatry. 2012 May 29;2:e126
pubmed: 22832970
Am J Alzheimers Dis Other Demen. 2018 May;33(3):153-165
pubmed: 29338302
J Mol Diagn. 2017 Nov;19(6):848-856
pubmed: 28807811
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
Am J Hum Genet. 2019 Apr 4;104(4):685-700
pubmed: 30929737
Clin Epigenetics. 2018 Feb 14;10:21
pubmed: 29456765
Am J Hum Genet. 2017 May 4;100(5):725-736
pubmed: 28475857