In This Issue

Abstract

Noninvasive prenatal screening (NIPS) of cell-free DNA from maternal serum enables detection of fetal aneuploidies. Although the screening typically aims to uncover viable, fetal trisomies, the analysis can also detect maternal copy-number variations (CNVs) that may be clinically actionable. In this issue, Brison and colleagues report a review of cases in which NIPS revealed maternal CNVs involving the DMD gene. Loss-of-function variants in the DMD gene can lead to dystrophinopathies, including Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder. The researchers examined NIPS results from more than 26,000 pregnant women who underwent the screening at the Center for Human Genetics in Leuven, Belgium, between 1 July 2017 and 30 June 2018. The analysis detected 16 maternal CNVs in the DMD gene, which corresponds to an incidence of 1 in 1632 pregnant women. Using DNA extracted from maternal white blood cells, the scientists validated the size and position of all 16 maternal CNVs by chromosomal microarray analysis. Phenotypic databases allowed correct interpretation and classification of variants in nine families. Of the remaining five detected variants, segregation analysis enabled classification of two. A recurrent in-frame duplication of exons 10–27 in unrelated women from three families was also present in clinically unaffected adult male relatives, leading Brison and team to classify this variant as likely benign. Paternal inheritance of an in-frame deletion in exons 54–55 in another family allowed classification of this variant as likely benign as well. Finally, the researchers classified a novel out-of-frame duplication of exons 51–62 for which segregation analysis was uninformative as likely pathogenic for DMD. Variants detected in two families remain unclassified. The authors conclude that NIPS can provide relevant and clinically actionable DMD variants to the mother and present a strategy for return of results. V. L. Dengler, News Editor Scientists uncover links between lysosomal storage diseases and cancer