Somatic DNA Variants in Epilepsy Surgery Brain Samples from Patients with Lesional Epilepsy

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 815 - 815

Опубликована: Янв. 19, 2025

Epilepsy affects 50 million people worldwide and is drug-resistant in approximately one-third of cases. Even when a structural lesion identified as the epileptogenic focus, understanding underlying genetic causes crucial to guide both counseling treatment decisions. Both somatic germline DNA variants may contribute itself and/or influence severity symptoms. We therefore used whole exome sequencing (WES) search for potentially pathogenic brain samples from children with lesional epilepsy who underwent surgery. WES was performed on 20 paired extracted tissue reference same patient, such leukocytes or fibroblasts. The data were jointly analyzed using GATK Mutect2 identify single nucleotide (SNVs) insertions/deletions (InDels), which subsequently evaluated silico their disease-causing potential MutationTaster2021. known five patients (25%) variant allele frequencies (VAF) ranging 3–35% genes MTOR, TSC2, PIK3CA, FGFR1, PIK3R1 cortical malformations central nervous system (CNS) tumors. Depending VAF, we different methods Sanger sequencing, allele-specific qPCR, targeted ultra-deep (amplicon sequencing) confirm variant. In contrast usually straightforward confirmation variants, validation more challenging because current have limitations sensitivity, specificity, cost-effectiveness. our study, additional candidates VAFs 0.7–7.0% that could not be validated by an orthogonal method. This highlights importance validation, especially those very low frequencies.

Язык: Английский

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Somatic mosaicism and interneuron involvement in mTORopathies

Trends in Neurosciences, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Breaking Balance: Synaptic Interneuron Properties Shift the E-I Balance in FCD I Epilepsy

Epiliepsy currents/Epilepsy currents, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

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Язык: Английский

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