The biallelic pathogenic variants of TBCD gene were reported to be associated with severe degenerative encephalopathy accompanied with seizures previously.
We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin corpus callosum, developmental delay, intellectual disability, seizures, optic atrophy, and spastic quadriplegia.
Variable expressivity of a likely pathogenic variant in KCNQ2 in a three-generation pedigree presenting with intellectual disability with childhood onset seizures.
Mutations in the CDKL5 gene have been associated with the early-onset seizure variant of Rett syndrome and mutations in FOXG1 have been associated with the congenital Rett syndrome variant.
In addition to a FOXG1 mutation in a patient with all core features of the congenital variant of RTT, we identified a missense (p.Ser240Thr) in CDKL5 in a patient who appeared to be seizure free.
Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization.
In seven patients with BNFCs and no recurrence of seizures, a novel two-base-pair deletion (1369del2) was identified within the coding sequence of the KCNQ2 gene.
In seven patients with BNFCs and no recurrence of seizures, a novel two-base-pair deletion (1369del2) was identified within the coding sequence of the KCNQ2 gene.
Based on seizure frequency at onset and cognitive outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2 encephalopathy to patients with moderate intellectual disability and/or infrequent seizures at onset.
Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A.
Several studies suggest that brain-derived neurotrophic factor (BDNF) can exacerbate seizure development during status epilepticus (S.E.) and subsequent epileptogenesis in the adult brain.
Epilepsy with mutation of the CDKL5 gene causes early seizures and is a variant of Rett syndrome (MIM (312750), which is reported typically as infantile spasms.
PRI-2191 alone had no effect on gene expression, but it enhanced the seizure-evoked expression of HSP-70, had an opposite effect on BDNF mRNA level and did not affect prepro-TRH mRNA level.
Individuals with the p.R168X mutation and heterozygous for the BDNF polymorphism were also at an increased risk of seizure onset (hazard ratio 5.3, 95% confidence interval 1.6-17.7) compared with those homozygous for the wild-type BDNF allele.
Evidence from experimental research shows that encephalopathy in TSC might have a genetic cause, and mTOR activation caused by TSC gene mutation can be directly responsible for the early appearance of seizures and encephalopathy.