Deep tissue sequencing improves genetic diagnostic yield in focal cortical dysplasia.

ABSTRACT: Focal cortical dysplasias (FCDs) are malformations of cortical development associated with drug-resistant focal epilepsy. We analysed surgical tissue from 28 consecutive cases recruited from adult and pediatric epilepsy surgery programs. We performed high-depth sequencing of lesional tissue, validated somatic variants using droplet digital PCR, and investigated genotype-phenotype correlations. A pathogenic or likely pathogenic variant was detected in 71% (n=20/28) of cases. Of these, six cases with FCDIIa or FCDIIb had germline variants in NPRL3 (n=4) or DEPDC5 (n=2). Somatic variants were identified in 50% (n=14/28) of cases. The genetic yield for FCDIIb was 85% of cases having a pathogenic mTOR pathway variant detected (n=12/14), and for FCDIIa 66% (n=6/9). This was achieve

SUBMITTER: Galea B 

PROVIDER: S-EPMC12668077 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature