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              <p>Primary brain calcification (PBC) is a dominantly inherited calcifying disorder of the brain. SLC20A2 loss-of-function variants account for the majority of families. Only one genomic deletion encompassing SLC20A2 and six other genes has been reported. We performed whole-exome sequencing (WES) in 24 unrelated French patients with PBC, negatively screened for sequence variant in the known genes SLC20A2, PDGFB, PDGFRB and XPR1. We used the CANOES tool to detect copy number variations (CNVs). We detected two deletions of exon 2 of SLC20A2 in two unrelated patients, which segregated with PBC in one family. We then reanalyzed the same series using a QMPSF assay including one amplicon in each exon of SLC20A2 and detected two supplemental partial deletions in two patients: one deletion of exon 4 and one deletion of exons 4 and 5. These deletions were missed by the first screening step of CANOES but could finally be detected after readjustment of bioinformatic parameters and use of a genotyping step of CANOES. This study reports the first partial deletions of SLC20A2 and strengthens its position as the major PBC-causative gene. It is possible to detect short CNVs from WES data, although the sensitivity of such tools should be evaluated in comparison with other methods. © 2016 Macmillan Publishers Limited, part of Springer Nature.</p>
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