Differential DNA methylation as a tool for noninvasive prenatal diagnosis (NIPD) of X chromosome aneuploidies

Floriana Della Ragione, Paola Mastrovito, Ciro Campanile, Anna Conti, Elisavet A. Papageorgiou, Maj A. Hultén, Philippos C. Patsalis, Nigel P. Carter, Maurizio D'Esposito

Research output: Contribution to journalArticlepeer-review

Abstract

The demographic tendency in industrial countries to delay childbearing, coupled with the maternal age effect in common chromosomal aneuploidies and the risk to the fetus of invasive prenatal diagnosis, are potent drivers for the development of strategies for noninvasive prenatal diagnosis. One breakthrough has been the discovery of differentially methylated cell-free fetal DNA in the maternal circulation. We describe novel bisulfite conversion- and methylation-sensitive enzyme digestion DNA methylation-related approaches that we used to diagnose Turner syndrome from first trimester samples. We used an Xlinked marker, EF3, and an autosomal marker, RASSF1A, to discriminate between placental and maternal blood cell DNA using real-time methylation-specific PCR after bisulfite conversion and real-time PCR after methylation-sensitive restriction digestion. By normalizing EF3 amplifications versus RASSF1A outputs, we were able to calculate sex chromosome/autosome ratios in chorionic villus samples, thus permitting us to correctly diagnose Turner syndrome. The identification of this new marker coupled with the strategy outlined here may be instrumental in the development of an efficient , noninvasive method of diagnosis of sex chromosome aneuploidies in plasma samples.

Original languageEnglish
Pages (from-to)797-807
Number of pages11
JournalJournal of Molecular Diagnostics
Volume12
Issue number6
DOIs
Publication statusPublished - Nov 1 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

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