Methylation pattern at the KvDMR in a child with Beckwith–Wiedemann syndrome conceived by ICSI

Gomes, M.V.; Gomes, Carolina Cavaliéri; Pinto, Wladimir B.V.R.; Ramos, Ester Silveira

doi:10.1002/ajmg.a.31628

Cited by 37 publications

(31 citation statements)

References 27 publications

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“…Larger fertility treatment subgroups will be necessary to ensure a sufficient number of informative individuals [heterozygous for Singlenucleotide polymorphism (SNP)] for proper LOI analyses. Interestingly, several case studies have reported solely methylation data while no allele-specific gene expression was examined which would be necessary to define LOI (Orstavik et al, 2003;Rossignol et al, 2006;Gomes et al, 2007;Kagami et al, 2007;Douzgou et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…However, several candidate imprinted loci have been implicated in various SRS patient cases, including GRB10, MEST and H19/IGF2 (Preece et al, 1999; Monk et al, 2000;Kobayashi et al, 2001;Kagami et al, 2007). Case -control studies have suggested that patients with BWS (Rossignol et al, 2006;Gomes et al, 2007), AS (Cox et al, 2002;Orstavik et al, 2003) and SRS (Kagami et al, 2007;Douzgou et al, 2008) were more likely conceived with ART than healthy individuals suggesting that reproductive technologies contribute to the disruption of imprint methylation marks (e.g. loss of methylation at DMRs at the normally methylated allele) but these studies were compromised by limited sample sizes.…”

Section: Introductionmentioning

confidence: 99%

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Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort

2012

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study question: Do fertility treatments, including ovulation induction (OI), alter epigenetic mechanisms such as DNA methylation at imprinted loci? summary answer: We observed small but statistically significant differences in certain imprinting control regions (ICRs) based on the method of conception, however, these small changes in methylation did not correlate to the overall transcriptional levels of the genes adjacent to the ICRs (such as KCNQ1 and SNRPN).what is known and what this paper adds: Assisted reproductive technology (ART) has been associated with an increase in the risk of rare childhood disorders caused by loss of imprinting (LOI). This study provides novel epigenetic analyses on infants conceived by OI and examines how methylation levels correlate with gene expression.design: Data and biospecimens used in this study were from 147 participants of the Epigenetic Birth Cohort comprising 1941 mother-child dyads recruited between June 2007 and June 2009 at the Department of Obstetrics, Gynecology and Reproductive Biology at Brigham and Women's Hospital (BWH) in Boston, MA, USA. Wilcoxon rank-sum tests were used to examine the differences in median percent methylation at each differentially methylated region (DMR) between the spontaneous conception control group and the fertility treatment groups (OI and IVF). participants and setting: For each woman who reported IVF we selected a woman who conceived spontaneously matched on age (+2 years). To increase efficiency, we matched the same controls from the spontaneously conceived group to participants who reported OI. If an appropriate control was not identified that had been previously matched to an IVF participant, a new control was selected. The final analytic sample consisted of 61 spontaneous, 59 IVF and 27 OI conceptions.main results and the role of chance: No functionally relevant differences in methylation levels were observed across five (out of six) imprinted DMRs in either the placenta or cord blood of infants conceived with OI or IVF compared with infants conceived spontaneously. While KCNQ1, SNRPN and H19 DMRs demonstrated small but statistically significant differences in methylation based on the method of conception, expression levels of the genes related to these control regions only correlated with the methylation levels of H19.bias, confounding and other reasons for caution: Limitations of our study include the limited sample size, lack of information on OI medication used and culture medium for the IVF procedures and underlying reasons for infertility among OI and IVF patients. We did not perform allele-specific expression analyses and therefore cannot make any inferences about LOI.generalizability to other populations: These results are likely to be generalizable to non-Hispanic white individuals in populations with similar ART and fertility treatments.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort

2012

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“…The 25-µl PCR reaction mix contained 2X PCR HotStart Premix buffer (Takara, Tokyo, Japan), 0.5 µM primer-M forward and 0.5 µM primer-M reverse in the PCR reaction amplifying the methylated imprint specifically or 0.5 µM primer-U forward and 0.5 µM primer-U reverse in the unmethylated PCR, and 2 µl of bisulfite-modified DNA. Primer sequences for KvDMR1 (21), MEST (22), SNRPN (23), MEG3 (24), XIST (25), and TNDM (26) were used as described, and PCR programs were summarized in Table I. PCR products were separated on a 2% agarose gel, stained with ethidium bromide and visualized under UV illumination.…”

Section: Sodium Bisulfite Treatment and Methylation-specific Pcrmentioning

confidence: 99%

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Zheng

Shi

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Assisted reproductive technology (ART) includingin vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been shown to be associated with abnormal genomic imprinting, thus increasing the incidence of imprinting disorders such as Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS) in ART-conceived children. Furthermore, a recent study described abnormal DNA methylation in clinically normal children conceived by ART. However, data from different studies are conflicting or inconclusive. This study examined DNA methylation patterns of multiple imprinted genes in children born after ART to primarily evaluate the impact of ART on genomic imprinting. A total of 101 newborns conceived by ART (40 ICSI and 61 IVF) and 60 naturally conceived newborns were involved in our study. After obtaining the approval of the Institutional Ethics Committee, umbilical cord blood was collected from each infant. Genomic DNA was isolated from each blood sample and treated using sodium bisulfite. Subsequently, using methylation-specific PCR (MS-PCR), we analyzed six differentially methylated regions (DMRs) including KvDMR1, SNRPN, MEST, MEG3, TNDM and XIST. Meanwhile, information regarding twin pregnancies, gestational age, and birth weight of the neonates was documented. None of the cases presented with phenotypic abnormalities. Children conceived by ART were more likely to have low birth weight and to be born before term, compared with children conceived spontaneously. However, 7 months to 3 years of clinical follow-up showed that none of the children had clinical symptoms of any imprinting diseases. Furthermore, the MS-PCR results showed that all 161 children had normal DNA methylation patterns at six DMRs despite the different mode of conception. Our data did not indicate a higher risk of DNA-methylation defects in children born after ART. However, further studies using quantitative methods are needed to confirm these results.

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“…Several investigations have indeed linked assisted reproductive technologies (ARTs) such as ovarian stimulation and in vitro embryo culture to aberrant imprinting in different species [4]. Furthermore, evidence has suggested an increased incidence of rare human imprinting disorders such as Beckwith-Wiedemann syndrome in children conceived after the use of ARTs [5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Dynamics of Imprinted DNA Methylation and Gene Transcription for Imprinting Establishment in Mouse Oocytes in Relation to Culture Duration Variability1

Anckaert

Sánchez

Billooye

et al. 2013

Biology of Reproduction

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Several studies have linked assisted reproductive technologies to aberrant imprinting. We previously showed that 12-day in vitro follicle culture supports normal imprinting establishment in mouse oocytes. The aim of the present study was to assess whether shortened in vitro follicle growth (8 days of culture compared with 12 days, as a model for human in vitro maturation) or preovulatory intrafollicular oocyte "aging" in culture (14 days of culture) leads to imprinting mutations in oocytes. Limiting-dilution bisulphite sequencing showed that shortened in vitro follicle growth (8 days) does not induce oocyte epimutations at the imprinted Snrpn and Mest genes. In contrast, extension of oocyte residence in large unluteinized follicles in vitro was associated with a low level (1 of 54 alleles) of epimutations for Mest but not for Snrpn. The latter condition may occur during controlled ovarian stimulation where the oocyte growth phase may be extended for several days. Furthermore, we studied the dynamics during follicle culture of transcript levels for genes previously shown to be essential for imprinting establishment in oocytes, including Dnmt3a, Dnmt3L, and Zfp57. Oocyte total mRNA levels during in vitro follicle culture showed the timely shutdown in transcription at the antral follicle stage, and total mRNA levels were comparable to those of in vivo grown equine chorionic gonadotropin-stimulated oocytes.

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Methylation pattern at the KvDMR in a child with Beckwith–Wiedemann syndrome conceived by ICSI

Cited by 37 publications

References 27 publications

Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort

Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort

Study of DNA methylation patterns of imprinted genes in children born after assisted reproductive technologies reveals no imprinting errors: A pilot study

Dynamics of Imprinted DNA Methylation and Gene Transcription for Imprinting Establishment in Mouse Oocytes in Relation to Culture Duration Variability1

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