Genetic Screening for Epileptic Spasms

We used molecular inversion probes to capture all exons and 5 base pairs of flanking intronic DEPDC5 sequence; next-generation sequencing and data analysis were performed as described previously in 130 patients with epileptic spasms of unknown etiology.^{15 (link),18 (link)} Known epileptic encephalopathy genes had been excluded in many cases (unpublished data, Carvill et al., January 2015).^{18 (link)}We considered only nonsynonymous, splice site, or frameshift variants that were present at an allele frequency <1% in ∼61,000 exomes of the Exome Aggregation Consortium (ExAC) data set (to exclude single nucleotide polymorphisms) (http://exac.broadinstitute.org/) for further analysis and performed segregation analysis for these rare variants in available family members. We considered truncating variants to be pathogenic and missense variants that were either inherited from an affected parent or arose de novo to be possibly pathogenic. Maternity/paternity was confirmed using the PowerPlex S5 system (Promega, Madison, WI). We included an additional novel DEPDC5 case, identified through commercial genetic testing (D:II:1), and additional phenotypic data on cousins from our earlier report (family E).^{1 (link)}