Figure 1.

Congenital hypoplastic anemia caused by compound heterozygosity for a CECR1 missense mutation and exon 7 deletion. (A) Pedigree. (B) Plot of WGS coverage depth on Chromosome 22p of the proband suggests an ∼2-kb maternally inherited CECR1 deletion (black arrows). (C) Visualization of mapped reads of the proband (via the Integrated Genomics Viewer) in the region of the deletion event. The red arrow denotes the position of the right breakpoint. CECR1 exon 7 and Alu repeat sequences are shown at the bottom in blue. Colored reads indicate pairs with anomalous insert sizes or reads with a mate mapping to a repetitive sequence on another chromosome. Dark red reads indicate a deletion event. The left breakpoint is embedded in repetitive Alu-derived sequences and thus was identified by only two of the four calling algorithms used. Failure to precisely define the breakpoint locations caused this copy-number variant to be filtered away by a quality-control step in our standard analytical pipeline for WGS.