From targeted SCN1A analysis to whole exome sequencing: clinical utility and novel genetic findings in a Hungarian paediatric epilepsy cohort.

Progressive broadening of genomic interrogation, from targeted SCN1A sequencing to gene panels and whole exome sequencing, with MLPA for SCN1A copy number analysis.

431 individuals with heterogeneous paediatric-onset epilepsy phenotypes were assessed between 2018 and 2024 at the Department of Medical Genetics of the University of Pécs, using Sanger sequencing, targeted epilepsy gene panels, whole exome sequencing and MLPA for SCN1A copy number analysis. Thirty-six pathogenic or likely pathogenic SCN1A variants were identified, including 15 not previously reported. Nine novel variants were also detected in 12 additional epilepsy-associated genes, and exome analysis revealed 6 novel variants in 19 genes. Diagnostic yield was proportional to the breadth of genomic interrogation, underscoring the genetic heterogeneity of these epilepsies and the clinical utility of both panels and exome sequencing, particularly in complex phenotypes.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The finding is expected but worth documenting over a continuous six-year series: the broader the interrogation, the higher the yield, which in 2026 argues for entering directly with exome sequencing rather than stacking successive targeted tests over years. Major methodological regret: comparative yields by strategy are not quantified, depriving the reader of exactly the argument needed to reorganise a diagnostic pathway. Retaining MLPA for SCN1A copy number variation is a useful reminder — many exome pipelines still miss them.

Analysis by Dr Thibaut Benquey