Molecular genetic advances in inherited focal epilepsies have pinpointed their genetic heterogeneity and the fact that they are mediated by different biological pathways: ion channel subunit genes have been linked to ADNFLE (CHRNA4, CHRNA2, CHRNB2, and KCNT1, encoding, respectively, the α4, α2, and β2 subunits of the neuronal nicotinic acetylcholine receptor, and a potassium channel subunit); neuronal secreted protein (LGI1-encoding epitempin) has been linked to autosomal dominant epilepsy with auditory features; and mTORC1-repressor DEPDC5 (DEP domain-containing protein 5) gene has recently been reported in a broad spectrum of inherited focal epilepsies (ADNFLE, FTLE, FFEVF).
The present case of hypochondroplasia and FGFR3 mutation in Asn540Lys associated with characteristic abnormalities involving bilaterally medial temporal lobe structures, probable hippocampal cortex focal dysplasia, and early onset of focal epilepsy underscores the possibility of a rare syndrome.
Thus, we screened SCN1A mutations in 13 families with partial epilepsy with antecedent febrile seizures (PEFS+) using denaturing high-performance liquid chromatography and sequencing.
The results of the present study indicate that the rs3812718 SNP in the SCN1A gene is significantly associated with the retention rate of CBZ monotherapy in Chinese Han patients with focal epilepsy.
We describe the variable clinical phenotypes that include the self-limited focal epilepsies of childhood, present in a large GEFS+ family, segregating a heterozygous SCN1A missense variant.
Lack of association of SCN2Ars17183814 polymorphism with the efficacy of lamotrigine monotherapy in patients with focal epilepsy from Herzegovina area, Bosnia and Herzegovina.
Molecular genetic advances in inherited focal epilepsies have pinpointed their genetic heterogeneity and the fact that they are mediated by different biological pathways: ion channel subunit genes have been linked to ADNFLE (CHRNA4, CHRNA2, CHRNB2, and KCNT1, encoding, respectively, the α4, α2, and β2 subunits of the neuronal nicotinic acetylcholine receptor, and a potassium channel subunit); neuronal secreted protein (LGI1-encoding epitempin) has been linked to autosomal dominant epilepsy with auditory features; and mTORC1-repressor DEPDC5 (DEP domain-containing protein 5) gene has recently been reported in a broad spectrum of inherited focal epilepsies (ADNFLE, FTLE, FFEVF).
The LGI1 gene has been implicated in the malignant progression of glioblastoma and it has also been genetically linked to a form of partial epilepsy (ADLTE).
The involvement of DEPDC5, NPRL2 and NRPL3 in about 10% of FEs is in contrast to the concept that specific seizure semiology points to the main involvement of a distinct brain area.
Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy.
Expert opinion: DEPDC5 is an attractive therapeutic target in focal epilepsy, as effects of DEPDC5 agonists would likely be anti-epileptogenic and more selective than currently available mTOR inhibitors.
A particular focus is DEPDC5, the first gene for nonlesional focal epilepsy likely to be relevant to sporadic patients with focal epilepsies and those from small families, in contrast to rare large families with autosomal dominant focal epilepsies.
In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies.
Restoration of phenotypic features by WT but not epilepsy-associated Depdc5 mutants, as well as by mTORC1 inhibition confirm the role of Depdc5 in the mTORC1-dependent molecular cascades, defining this pathway as a potential therapeutic target for <i>DEPDC5</i>-inherited forms of focal epilepsy.
Seven patients from 4 families with DEPDC5 mutations and focal epilepsy associated with FCD were recruited and investigated at the clinical, neuroimaging, and histopathological levels.