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

• DOI: 10.4161/epi.25812
• Publication Date: 2013-08-29T12:28:20Z
• Authors: Mariarosaria Calv...; 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
• Keywords: Beckwith–Wiedemann syndrome; Macroglossia

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