Exome sequencing was performed on genomic DNA from peripheral blood of 3 affected members (A/II-1, A/II-4, and A/II-9) of family A. Targeted exome sequencing, library preparation, capture (Human All exon kit V4+UTRs, 70 Mb, Agilent, Interactive Biosoftware, Rouen, France), sequencing, and variant detection and annotation were performed by IntegraGen (Evry, France) using a previously described procedure.12 Variants with low quality (<20) and low VQSLOD (logarithm of odds ratio that a variant is real vs not under the trained gaussian mixture model) (<0) were filtered out. Variants with a read depth >30 and allele read frequency >0.30 were filtered. High-quality variants were further filtered for those predicted to affect the protein-coding sequence (nonsense, missense, frameshift, or essential splice-site) and with a minor allele frequency (<1%) in the exome variant server (http://evs.gs.washington.edu/EVS/).
