Dataset Information

(Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith-Wiedemann syndrome.

ABSTRACT: BACKGROUND:Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder caused by defects at the 11p15.5 imprinted region. Many cases of female monozygotic (MZ) twins discordant for BWS have been reported, but no definitive conclusions have been drawn regarding the link between epigenetic defects, twinning process, and gender. Here, we report a comprehensive characterization and follow-up of female MZ twins discordant for BWS. METHODS:Methylation pattern at 11p15.5 and multilocus methylation disturbance (MLID) profiling were performed by pyrosequencing and MassARRAY in placental/umbilical cord samples and postnatal tissues. Whole-exome sequencing was carried out to identify MLID causative mutations. X-chromosome inactivation (XCI) was determined by HUMARA test. RESULTS:Both twins share KCNQ1OT1:TSS-DMR loss of methylation (LOM) and MLID in blood and the epigenetic defect remained stable in the healthy twin over time. KCNQ1OT1:TSS-DMRLOM was nonhomogeneously distributed in placental samples and the twins showed the same severely skewed XCI pattern. No MLID-causative mutations were identified. CONCLUSION:This is the first report on BWS-discordant twins with methylation analyses extended to extraembryonic tissues. The results suggest that caution is required when attempting prenatal diagnosis in similar cases. Although the causative mechanism underlying LOM remains undiscovered, the XCI pattern and mosaic LOM suggest that both twinning and LOM/MLID occurred after XCI commitment.

SUBMITTER: Fontana L

PROVIDER: S-EPMC7507324 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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(Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith-Wiedemann syndrome.

Fontana Laura L Bedeschi Maria F MF Cagnoli Giulia A GA Costanza Jole J Persico Nicola N Gangi Silvana S Porro Matteo M Ajmone Paola F PF Colapietro Patrizia P Santaniello Carlo C Crippa Milena M Sirchia Silvia M SM Miozzo Monica M Tabano Silvia S

Molecular genetics & genomic medicine 20200706 9

<h4>Background</h4>Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder caused by defects at the 11p15.5 imprinted region. Many cases of female monozygotic (MZ) twins discordant for BWS have been reported, but no definitive conclusions have been drawn regarding the link between epigenetic defects, twinning process, and gender. Here, we report a comprehensive characterization and follow-up of female MZ twins discordant for BWS.<h4>Methods</h4>Methylation pattern at 11p15.5 and multilocus m ...[more]

PMID: 32627967

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Project description:BackgroundRheumatoid arthritis is a common autoimmune disorder influenced by both genetic and environmental factors. Epigenome-wide association studies can identify environmentally mediated epigenetic changes such as altered DNA methylation, which may also be influenced by genetic factors. To investigate possible contributions of DNA methylation to the aetiology of rheumatoid arthritis with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs.MethodsGenome-wide DNA methylation was assessed in 79 monozygotic twin pairs discordant for rheumatoid arthritis using the HumanMethylation450 BeadChip array (Illumina). Discordant twins were tested for both differential DNA methylation and methylation variability between rheumatoid arthritis and healthy twins. The methylation variability signature was then compared with methylation variants from studies of other autoimmune diseases and with an independent healthy population.ResultsWe have identified a differentially variable DNA methylation signature that suggests multiple stress response pathways may be involved in the aetiology of the disease. This methylation variability signature also highlighted potential epigenetic disruption of multiple RUNX3 transcription factor binding sites as being associated with disease development. Comparison with previously performed epigenome-wide association studies of rheumatoid arthritis and type 1 diabetes identified shared pathways for autoimmune disorders, suggesting that epigenetics plays a role in autoimmunity and offering the possibility of identifying new targets for intervention.ConclusionsThrough genome-wide analysis of DNA methylation in disease-discordant monozygotic twins, we have identified a differentially variable DNA methylation signature, in the absence of differential methylation in rheumatoid arthritis. This finding supports the importance of epigenetic variability as an emerging component in autoimmune disorders.

Dataset Information

(Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith-Wiedemann syndrome.

Publications

(Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith-Wiedemann syndrome.

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