Journal Article

Maternal copy-number variations in the DMD gene as secondary findings in noninvasive prenatal screening

Van Esch, Hilde, Devriendt, Koenraad, De Waele, Liesbeth, Storms, Jazz, Goemans, Nathalie, Claeys, Kristl G., Legius, Eric, Peeters, Hilde, Brison, Nathalie, de Ravel, Thomy, Van Den Bogaert, Kris, Dehaspe, Luc, Robert Vermeesch, Joris, Villela, Darine, Race, Valerie

2019

Overview

Purpose Noninvasive prenatal screening (NIPS) using genome sequencing also reveals maternal copy-number variations (CNVs). Those CNVs can be clinically actionable or harmful to the fetus if inherited. CNVs in the DMD gene potentially causing dystrophinopathies are among the most commonly observed maternal CNVs. We present our experience with maternal DMD gene CNVs detected by NIPS. Methods We analyzed the data of maternal CNVs detected in the DMD gene revealed by NIPS. Results Of 26,123 NIPS analyses, 16 maternal CNVs in the DMD gene were detected (1/1632 pregnant women). Variant classification regarding pathogenicity and phenotypic severity was based on public databases, segregation analysis in the family, and prediction of the effect on the reading frame. Ten CNVs were classified as pathogenic, four as benign, and two remained unclassified. Conclusion NIPS leverages CNV screening in the general population of pregnant women. We implemented a strategy for the interpretation and the return of maternal CNVs in the DMD gene detected by NIPS.

• Publisher: Nature Publishing Group US,Elsevier Limited
• Subject: Adult / Biomedical and Life Sciences / Biomedicine / DNA Copy Number Variations - genetics / Dystrophin - genetics / Dystrophin - metabolism / Female / Fetus / Human Genetics / Humans / Incidental Findings / Laboratory Medicine / Noninvasive Prenatal Testing - ethics / Noninvasive Prenatal Testing - methods / Pregnancy / Prenatal Diagnosis - ethics / Prenatal Diagnosis - methods / Sequence Analysis, DNA - ethics / Sequence Analysis, DNA - methods / Whole genome sequencing