Deep tissue sequencing improves genetic diagnostic yield in focal cortical dysplasia

B Galea; J Reid; S Gooley; T Witkowski; T Lane; S Macdonald; TE Green; Z Ye; T Adikari; K Bulluss; SA Mullen; CA Bennett; B Forster; G Bradshaw; W Lin; W De Silva; RB Ramirez; S Khoshkhoo; S Gupta; M Krivanek; K Kothur; D Gill; K Pope; G Gillies; M Coleman; WS Lee; SM Stephenson; W Maixner; AS Harvey; E Macdonald-Laurs; KB Howell; C D'Arcy; PJ Lockhart; RJ Leventer; RM Kalnins; J Clark; MF Bennett; M Bahlo; IE Scheffer; P Perucca; SF Berkovic; MS Hildebrand

Journal article

Deep tissue sequencing improves genetic diagnostic yield in focal cortical dysplasia

B Galea, J Reid, S Gooley, T Witkowski, T Lane, S Macdonald, TE Green, Z Ye, T Adikari, K Bulluss, SA Mullen, CA Bennett, B Forster, G Bradshaw, W Lin, W De Silva, RB Ramirez, S Khoshkhoo, S Gupta, M Krivanek Show all

Progress in Neuro Psychopharmacology and Biological Psychiatry | Published : 2026

DOI: 10.1016/j.pnpbp.2026.111920

Open access

Abstract

Focal cortical dysplasias (FCDs) are malformations of cortical development associated with drug-resistant focal epilepsy. We analyzed surgical tissue from 25 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 or amplicon sequencing, and investigated genotype-phenotype correlations. A pathogenic or likely pathogenic variant was detected in 64% (n = 16/25) of cases. Of these, five cases with FCDIIa or FCDIIb had germline variants in NPRL3 (n = 3) or DEPDC5 (n = 2). Somatic variants were identified in 44% (n = 11/25) of cases. The genetic yield for FCDIIb was ..

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