In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 8 ( 2023-8-18), p. e0290450-
Kurzfassung:
Imprinted genes are regulated by DNA methylation of imprinted differentially methylated regions (iDMRs). An increasing number of patients with congenital imprinting disorders (IDs) exhibit aberrant methylation at multiple imprinted loci, multi-locus imprinting disturbance (MLID). We examined MLID and its possible impact on clinical features in patients with IDs. Genome-wide DNA methylation analysis (GWMA) using blood leukocyte DNA was performed on 13 patients with Beckwith–Wiedemann syndrome (BWS), two patients with Silver–Russell syndrome (SRS), and four controls. HumanMethylation850 BeadChip analysis for 77 iDMRs (809 CpG sites) identified three patients with BWS and one patient with SRS showing additional hypomethylation, other than the disease-related iDMRs, suggestive of MLID. Two regions were aberrantly methylated in at least two patients with BWS showing MLID: PPIEL locus (chromosome 1: 39559298 to 39559744), and FAM50B locus (chromosome 6: 3849096 to 3849469). All patients with BWS- and SRS-MLID did not show any other clinical characteristics associated with additional involved iDMRs. Exome analysis in three patients with BWS who exhibited multiple hypomethylation did not identify any causative variant related to MLID. This study indicates that a genome-wide approach can unravel MLID in patients with an apparently isolated ID. Patients with MLID showed only clinical features related to the original IDs. Long-term follow-up studies in larger cohorts are warranted to evaluate any possible phenotypic consequences of other disturbed imprinted loci.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0290450
DOI:
10.1371/journal.pone.0290450.g001
DOI:
10.1371/journal.pone.0290450.g002
DOI:
10.1371/journal.pone.0290450.g003
DOI:
10.1371/journal.pone.0290450.t001
DOI:
10.1371/journal.pone.0290450.t002
DOI:
10.1371/journal.pone.0290450.t003
DOI:
10.1371/journal.pone.0290450.s001
DOI:
10.1371/journal.pone.0290450.s002
DOI:
10.1371/journal.pone.0290450.s003
DOI:
10.1371/journal.pone.0290450.s004
DOI:
10.1371/journal.pone.0290450.s005
DOI:
10.1371/journal.pone.0290450.s006
DOI:
10.1371/journal.pone.0290450.s007
DOI:
10.1371/journal.pone.0290450.r001
DOI:
10.1371/journal.pone.0290450.r002
DOI:
10.1371/journal.pone.0290450.r003
DOI:
10.1371/journal.pone.0290450.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2267670-3
