Identification of rare maternal copy number variants by genome-wide analysis of noninvasive prenatal screening data in 113,017 pregnant women.

Genome-wide analysis of noninvasive prenatal screening sequencing depth (10 kb bins, circular binary segmentation) to detect maternal CNVs

Sequencing data from noninvasive prenatal screening contain maternal genomic information that is rarely exploited. In 113,017 pregnant women, the genome was segmented into 10 kb bins and relative depth analysed by circular binary segmentation: 363,886 CNVs larger than 50 kb were detected in 101,779 participants and merged into 43,005 CNV regions. Reproducibility, assessed by comparing two successive pregnancies of the same participant, reached 90.18% for deletions and 88.07% for duplications. Overall, 78.13% of participants carried a region overlapping a protein-coding gene and 14.76% an OMIM gene; 246 novel CNV regions were described, 134 (54.47%) involving protein-coding genes, and 4,984 women (4.41%) were carriers of a CNV spanning a known pathogenic or likely pathogenic region, including the 22q11.2 region and the DMD gene.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

These maternal CNVs are secondary findings obtained without any additional sampling, and 4.41% is not marginal at the scale of a screening programme: carrying a DMD deletion or a 22q11.2 deletion changes counselling for the current pregnancy and for subsequent ones. Nothing here, however, is confirmed by a reference technique on maternal DNA, and no phenotypic data accompany these carriers. Returning such information requires a confirmation and consent pathway that most programmes do not have: the question raised is as much regulatory as technical.

Analysis by Dr Thibaut Benquey