Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome

Mariarosaria Calvello, Silvia Tabano, Patrizia Colapietro, Silvia Maitz, Alessandra Pansa, Claudia Augello, Faustina Lalatta, Barbara Gentilin, Filippo Spreafico, Luciano Calzari, Daniela Perotti, Lidia Larizza, Silvia Russo, Angelo Selicorni, Silvia M. Sirchia, Monica Miozzo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p <0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75-86%) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55-59%) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD.

Original languageEnglish
Pages (from-to)1053-1060
Number of pages8
JournalEpigenetics
Volume8
Issue number10
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Beckwith-Wiedemann Syndrome
DNA Methylation
Phenotype
Methylation
Uniparental Disomy
Umbilical Hernia
Macroglossia
Epigenomics
Neoplasms
Fetus
Chromosomes

Keywords

  • BWS
  • DNA methylation
  • Genomic imprinting
  • Pyrosequencing
  • UPD

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome. / Calvello, Mariarosaria; Tabano, Silvia; Colapietro, Patrizia; Maitz, Silvia; Pansa, Alessandra; Augello, Claudia; Lalatta, Faustina; Gentilin, Barbara; Spreafico, Filippo; Calzari, Luciano; Perotti, Daniela; Larizza, Lidia; Russo, Silvia; Selicorni, Angelo; Sirchia, Silvia M.; Miozzo, Monica.

In: Epigenetics, Vol. 8, No. 10, 10.2013, p. 1053-1060.

Research output: Contribution to journalArticle

Calvello, M, Tabano, S, Colapietro, P, Maitz, S, Pansa, A, Augello, C, Lalatta, F, Gentilin, B, Spreafico, F, Calzari, L, Perotti, D, Larizza, L, Russo, S, Selicorni, A, Sirchia, SM & Miozzo, M 2013, 'Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome', Epigenetics, vol. 8, no. 10, pp. 1053-1060. https://doi.org/10.4161/epi.25812
Calvello, Mariarosaria ; Tabano, Silvia ; Colapietro, Patrizia ; Maitz, Silvia ; Pansa, Alessandra ; Augello, Claudia ; Lalatta, Faustina ; Gentilin, Barbara ; Spreafico, Filippo ; Calzari, Luciano ; Perotti, Daniela ; Larizza, Lidia ; Russo, Silvia ; Selicorni, Angelo ; Sirchia, Silvia M. ; Miozzo, Monica. / Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome. In: Epigenetics. 2013 ; Vol. 8, No. 10. pp. 1053-1060.
@article{afb5756d68554104b5ed2e4d3f72a38b,
title = "Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome",
abstract = "Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p <0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75-86{\%}) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55-59{\%}) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD.",
keywords = "BWS, DNA methylation, Genomic imprinting, Pyrosequencing, UPD",
author = "Mariarosaria Calvello and Silvia Tabano and Patrizia Colapietro and Silvia Maitz and Alessandra Pansa and Claudia Augello and Faustina Lalatta and Barbara Gentilin and Filippo Spreafico and Luciano Calzari and Daniela Perotti and Lidia Larizza and Silvia Russo and Angelo Selicorni and Sirchia, {Silvia M.} and Monica Miozzo",
year = "2013",
month = "10",
doi = "10.4161/epi.25812",
language = "English",
volume = "8",
pages = "1053--1060",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Taylor and Francis Inc.",
number = "10",

}

TY - JOUR

T1 - Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome

AU - Calvello, Mariarosaria

AU - Tabano, Silvia

AU - Colapietro, Patrizia

AU - Maitz, Silvia

AU - Pansa, Alessandra

AU - Augello, Claudia

AU - Lalatta, Faustina

AU - Gentilin, Barbara

AU - Spreafico, Filippo

AU - Calzari, Luciano

AU - Perotti, Daniela

AU - Larizza, Lidia

AU - Russo, Silvia

AU - Selicorni, Angelo

AU - Sirchia, Silvia M.

AU - Miozzo, Monica

PY - 2013/10

Y1 - 2013/10

N2 - Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p <0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75-86%) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55-59%) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD.

AB - Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p <0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75-86%) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55-59%) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD.

KW - BWS

KW - DNA methylation

KW - Genomic imprinting

KW - Pyrosequencing

KW - UPD

UR - http://www.scopus.com/inward/record.url?scp=84884967377&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884967377&partnerID=8YFLogxK

U2 - 10.4161/epi.25812

DO - 10.4161/epi.25812

M3 - Article

VL - 8

SP - 1053

EP - 1060

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

IS - 10

ER -