text string | label int64 | pmid string |
|---|---|---|
Safety is one of the main concerns regarding mTOR inhibitor administration to young children and infants. | 1 | 37085686 |
However, how human microglia interacts with human neurons to regulate hyperexcitability mediated by epilepsy-causing genetic mutation found in human patients remains unknown. | 1 | 37961213 |
Albeit the heterogeneity of variant and phenotype has been summarized, a convincible explanation for this genotype-phenotype heterogeneity still lacked. | 1 | 36970538 |
However, ES has been less powerful in detecting structural variations (SVs) that involve intronic, GC-rich or repetitive regions than detecting single-nucleotide variants (SNVs) (Zhao et al, 2021; Marwaha et al, 2022). | 0 | 37286232 |
This finding could be explained by the fact that laminin-α2 binds with high affinity to the dystrophin-glycoprotein complex and to integrins through the LG-domain [23]. | 0 | 37182895 |
Clinical consequences of mTORC1 upregulation may be amenable to tailored treatment with mTOR inhibitors, although data on efficacy are inconclusive so far.
13
A clinical trial on an international scale would be needed to draw conclusions. | 1 | 37263295 |
Functional studies investigating the effect of such missense variants, quantifying mTORC1 activity, would help understand their role in GATORopathies. | 1 | 37491868 |
Most patients in this study continued the treatment at the end of data collection, so seizure recurrence assessment in a long-term follow-up after mTORi cessation was impossible. | 1 | 37085686 |
Perhaps given the complexity of SCN2A-related clinical phenotypes and that physiological function of SCN2A is developmentally regulated, complex patterns of variant channel dysfunction are not unexpected. | 0 | 37578743 |
In addition, considering the retrospective nature of this study, our data are heterogeneous in terms of age, timing/frequency and type of testing. | 0 | 37700749 |
Although haplotype analysis had not been performed, we speculate that c.1255del might be a founder variant in the Brazilian population. | 0 | 37182895 |
And the correlation of X inactivation and PCDH19-FE phenotype may also be partly explained by this hypothesis. | 0 | 36970538 |
Furthermore, contrary to the loss function hypothesis of PCDH19, the cellular interference theory indicated that clinical manifestations may be related to abnormal communication between normal and mutant cells (28). | 0 | 36970538 |
Various ASMs were trialed in the literature, with different combinations, making it difficult to draw conclusions regarding which ASM is best for ST3GAL3‐related DEE. | 1 | 37067065 |
Further prospective clinical trials should be conducted to determine the efficacy of mTOR inhibitors on epilepsy in patients with TSC under the age of 2 years. | 1 | 37085686 |
The patient’s exercise capacity had improved, and improvements in autism symptoms were not obvious. | 0 | 37026922 |
By extension, the Genic Causality score is more likely to be underestimated for drugs that are less studied, as their modes of action are less analyzed and, hence, knowledge of the proteins changed in function by them is less complete. | 0 | 36196775 |
As for the mechanism of the existence of asymptomatic carriers, the penetrance rate and X-inactivation are potential influencing factors. | 0 | 36970538 |
Although most types of CDG show cerebral and/or cerebellar atrophy on neuroimaging, these findings have not been associated with ST3GAL3 pathogenic variants to date. | 1 | 37067065 |
Due to the limited data available on mTOR inhibitor therapy in non-TSC epileptic patients,
6
7
we present the clinical management of a patient with intractable epilepsy with skin hypopigmentation and a
DEPDC5
variant. | 1 | 37263295 |
Furthermore, we suggest the administration of SCB for patients with a distinct phenotype of PRRT2‐related epilepsy at the initial presentation. | 0 | 36775847 |
More studies are needed to confirm the pathogenicity of this novel variant to establish the effective care, management, and genetic counselling of affected individuals. | 1 | 37498161 |
Regarding behavioral disorders, data from the literature may be misleading. Few authors have properly analyzed these features, reported as aggressive or oppositional behaviors with psychiatric traits. | 1 | 37700749 |
However, the factors influencing the up-regulation of Fut8 were still unknown, such as initial patient clinical characteristics and ASMs. | 1 | 37053181 |
Furthermore, our results illustrate a robust behavioral and electrophysiological phenotype that can be used for future in vivo single-unit electrophysiological experiments conducted over periods of weeks to months with the intention of gaining mechanistic insights into behaviors relevant to mood symptoms seen in human ... | 1 | 38123552 |
The lack of age dependence suggests that the reactive production of GFAP by astrocytes is not specific to a particular age group and supports our hypothesis of a common pathogenesis of FCD-associated temporal lobe DRE in both children and adults. | 0 | 37833937 |
Additionally, the severity of ID was also seldom detailed in the literature, and when reported, it ranged from mild to moderate in most cases. | 0 | 37700749 |
In this study, we employed a series of bioinformatics analyses and identified miR-30b-5p as a potential upstream regulator of GRIN2A, interfering with EP progression. | 0 | 37016703 |
These findings may expand our understanding of the phenotype and genotype of PRRT2‐related epilepsy and enable early patient recognition. | 0 | 36775847 |
Therefore, GRIN2A-mediated signaling pathways warrant further research. | 1 | 37016703 |
Despite the different locations of the two missense variants in FGF12, p.(Glu87Lys) in patient 2 and p.(Pro149Gln) likely lead to the loss of binding ability to NaVs. | 0 | 37286232 |
While potential mechanisms and pathways (e.g., microglia sensing of excessive ATP, UDP, etc) underlying the increase in Ca2+ signal need to be further elucidated in follow-up studies, our current work extends the earlier observations described in rodent models to a human cell context. | 1 | 37961213 |
We attributed smaller current density to a cell-selection bias inherent with manual patch-clamp recording, and the slower inactivation kinetics may be explained by a greater degree of series resistance compensation feasible with manual patch clamp due to lower access resistance. | 0 | 37578743 |
In this study, we demonstrate successful use of automated patch-clamp recording to determine the functional properties of several SCN2A variants expressed in two splice isoforms. | 0 | 37578743 |
Therefore, missense variants located in the β-propeller domain could affect the interaction of PIGT with the active site of PIGK, leading to the observed severe phenotype. | 0 | 36970549 |
The genotype-phenotype correlation needs more cases to further elucidate in the future.In summary, this study suggested that SZT2 variants were potentially associated with partial epilepsy with favorable outcomes without NDD, expanding the phenotypic spectrum of SZT2. | 1 | 37213690 |
In the last few years, there has been a marked increase in the number of identified variants, yet no clear genotype–phenotype correlation has been identified. | 1 | 38116105 |
Luo et al. (3) reported that seven family members carrying heterozygous mutations in the PRRT2 gene had no clinical symptoms associated with PRRT2-related disorders, suggesting incomplete penetrance of the PRRT2 mutations. | 0 | 37228410 |
Our findings suggest a need to re-evaluate the simple binary classification of SCN2A variants and to engage in efforts to determine how variants with mixed properties promote neuronal dysfunction. | 1 | 37578743 |
Our findings suggest that these mutations are likely to result in autosomal recessive Metachromatic Leukodystrophy, exhibiting symptoms similar to those reported, with the possibility of minor variations among our patients (Shahzad et al., 2017; Shaimardanova et al., 2020; Amr et al., 2021). | 0 | 37359369 |
This indicated that the interplay among simultaneous variants at different sites in PCDH19 also probably impacted the intermolecular interaction of PCDH19 protein. | 0 | 36970538 |
According to a review (6), females usually have a less severe phenotype than males, and the occurrence of facial dysmorphism, microcephaly, hypotonia, growth retardation, and feeding difficulties is less frequent in females than males, but surprisingly, epilepsy is more commonly reported in females | 0 | 37427056 |
There were some missing data the from literature review, and not all cases had all the reported variables of interest available. | 0 | 37067065 |
We further explored the possibility of co-expression of VUS in CHRNB2 and the RBFOX1 deletion affecting the phenotype in the proband and her sister. | 0 | 37033539 |
Because of the poor control of the epilepsy symptoms in the refractory epilepsy group, clinicians are more inclined to increase the dosage and use multiple drugs for treatment. | 0 | 37053181 |
The main limitation is the small size of the sample and the lack of longitudinal data. | 0 | 37700749 |
The biological significance of the identified mutation, p.Gly1233Glu, in the context of cerebrovascular changes and its association with neurologic symptoms warrants further investigation to shed light on its clinical implications. | 1 | 38074064 |
Pathogenic variants in genes encoding KV subunits may exert one or more effects on the assembly, trafficking, or the kinetics or the voltage dependence of the opening‐closing‐inactivating transitions of the channel, thereby disturbing membrane excitability or action potentials, leading to neurological diseases. | 0 | 36318112 |
Additionally, two cases had ongoing seizures after surgery or ASMs but were treated effectively by receiving KD, suggesting that KD may be a potential option for patients of NPRL3-related epilepsy unresponsive to surgery or ASMs. However, given our limited cases, future studies need more patients with NPRL3-related epi... | 1 | 36937533 |
The current treatment of epilepsy with NPRL3 gene variants is lacking in specificity. | 0 | 36937533 |
However, studying the mechanisms of neuronal functioning in epilepsy necessitates understanding the mechanisms of glial functioning due to the close interaction between these components [12] | 0 | 37833937 |
Due to the heterogeneous phenotypic features of epilepsy involved in changes in the sequence and expression of multiple genes (instead of a single gene), as well as the modification and regulation of genes by multiple factors, gene co-expression network analysis may help to reveal the molecular regulatory mechanisms du... | 0 | 37033539 |
Collectively, miR-30b-5p may attenuate the proliferation of hippocampal neurons in magnesium-free conditions by targeting GRIN2A. | 0 | 37016703 |
In addition, six atypical cases with neonatal‐onset seizures and unremitting after 3 years of age were included to understand the expanded clinical spectrum of PRRT2‐related epilepsy. | 0 | 36775847 |
Although functional testing was not available for our sibling pair, it is hypothesized that both variants resulted in a lack of ST3GAL3 enzyme activity. | 0 | 37067065 |
However, the electroclinical phenotype of ST3GAL3‐related DEE has not been fully elucidated. | 1 | 37067065 |
These data suggest that these two disorders share mechanistic links. However, identifying such mechanisms has remained a challenge [6]. | 1 | 38123552 |
Therefore, in clinical cases of repeated brief afebrile bilateral tonic–clonic seizures at initial onset, PRRT2‐related epilepsy should be considered, and SCBs should be used for seizure control. | 0 | 36775847 |
Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated... | 0 | 37264743 |
Targeted therapies remain scarce. | 0 | 38081835 |
To date, 13 patients with PIGS variants have been identified with developmental delay, seizures, and hypotonia, and only one canonical splicing variant has been reported. | 0 | 37035392 |
Hence, many lack effective treatments. | 0 | 36196775 |
Patient 2 manifested tremors, suggesting that the phenotypic spectrum of biallelic FGF12-related disorder may be potentially related to tremors. | 0 | 37286232 |
Other studies in yeast also have demonstrated defective protein synthesis and sensitivity to rapamycin caused by the G70S mutation as well as other mutations not explored here | 0 | 37695913 |
The mechanisms by which PIGS variants and GPI-APs are linked to intellectual deficiency or epilepsy warrant further clarification. | 1 | 37035392 |
Hence, these drugs merit study in clinical trials for Dravet syndrome. | 1 | 36196775 |
Besides, the mutual interactions between different mutated amino acids may also exert an influence on the structure and function of PCDH19. | 0 | 36970538 |
It is unclear why our sibling pair had a milder phenotype, given the predicted loss of enzymatic activity in our sibling pair and at present time, precise genotype–phenotype relationships have not been established for ST3GAL3‐related DEE. | 1 | 37067065 |
Therefore, these pieces of evidence indicated that epilepsy surgery might be a suitable option for patients of NPRL3-related epilepsy with neuroimaging abnormalities, especially with FCD. | 0 | 36937533 |
The additional report of a generalized tonic–clonic seizure after a urinary tract infection in our patient may also suggest a role of bacterial pathogens in disease progression. | 1 | 37895210 |
Here we should highlight that one of the limitations of our study is the brief period of follow-up of our patient, who is only at the age of 2 years at the time of writing. | 0 | 36970549 |
Numerous DEE genes have been discovered thanks to advances in genomic diagnosis, yet putative molecular links between these disorders are unknown. | 1 | 38081835 |
This suggests that protein expression may vary with age, implying distinct patterns of expression in children with epilepsy. | 0 | 37833937 |
Additionally, the severity of ID was also seldom detailed in the literature, and when reported, it ranged from mild to moderate in most cases. | 0 | 37700749 |
All patients in our cohort had focal-onset seizures with or without impaired awareness, which may be a more difficult type of seizure for the family to identify. | 0 | 37182895 |
Future investigations of the cell surface expression or localization of SCN2A variants in neurons can test this hypothesis. | 1 | 37578743 |
Although it is difficult to draw precise conclusions regarding the most effective ASM treatment for ST3GAL3‐related DEE given the small numbers, this may depend on the seizure and epilepsy type. | 1 | 37067065 |
This study aimed to report a five-generation pedigree of seven female patients of PCDH19-FE and tried to explore whether two variants were correlated with PCDH19 protein structure and function alteration, and PCDH19-FE phenotype. | 0 | 36970538 |
Since all reported patients thus far have been of Caucasian/Polish origin and most harbor the same variant (p.Val528Met), the ability to draw definitive conclusions regarding the genotype–phenotype correlation remains limited. | 1 | 36970549 |
This specific gain‐of‐function feature is likely to underlie the neurological phenotype in our patients. | 0 | 36318112 |
So far, few functional studies have been performed. | 1 | 37275776 |
Overall, evidence robust enough to guide antiseizure medication (ASM) choices in genetic epilepsies remains limited to the more frequent conditions for which controlled trials and observational studies have been possible. | 0 | 34493617 |
Our evaluation of a cohort of disease-associated SCN2A variants revealed a spectrum of NaV1.2 dysfunction that was not easily parsed into the binary categories. | 0 | 37578743 |
We aimed to create a computational method to predict the efficacy of drugs for monogenic epilepsies, and to use the method to predict drugs for Dravet syndrome, as (1) it is the archetypal monogenic catastrophic epilepsy; (2) few antiseizure medications are efficacious in Dravet syndrome; predicting the effect of drugs... | 0 | 36196775 |
This study suggested that BSN was potentially a candidate gene of epilepsy. | 0 | 36600631 |
We cannot, however, exclude the possibility of occurrence of the myoclonus during wakefulness and activity, as has been described in mice older than 8 months in mixed background. | 0 | 38179183 |
A detailed analysis of the relationship between gene variants and clinical phenotypes has not been conducted yet. | 1 | 37099548 |
Thus, we cannot determine whether the MOF was caused by NEXMIF variant or sodium valproate. | 0 | 37427056 |
Moreover, there is no apparent pattern of drug efficacy across the cases with recorded drug treatment, where both ethnic and individual differences are present. | 1 | 37470039 |
To elucidate how GNB1 mutations cause neurodevelopmental disease in a physiological context, we generated a mouse model of the pathogenic missense variant, K78R. | 0 | 37275776 |
The mutation spectrum of the DHDDS gene in the Chinese population remains unclear. | 1 | 37881805 |
Considering the available experimental data, a recent study has additionally suggested that the luminal part of PIGT (73-427 aa) consists of a β-propeller domain with a central hole that regulates the access of substrate protein C-termini to the active site of the cysteine protease PIGK (19). | 0 | 36970549 |
In addition, the heterozygous missense variant, [c.446C>A p.(Pro149Gln)] (rs17852067), which has never been reported in individuals with epilepsy or in gnomAD, was previously identified in individuals with arrhythmia (Li et al, 2017). | 0 | 37286232 |
Furthermore, previous studies have shown that interictal EEGs in BFIE are usually normal, though some BFIEs may exhibit interictal focal epileptiform discharges, mostly originating in the parieto-occipital lobe and located in the frontotemporal region (12, 30, 31). | 0 | 37228410 |
We analyzed the clinical data and genetic variants of a PCDH19-FE pedigree, to explore the phenotype heterogeneity of PCDH19-FE and underlying mechanisms. | 0 | 36970538 |
It also underlies the importance of SETD1A mutation analysis in hypothyroid patients with epilepsy. | 0 | PMID not found |
However, there is compelling evidence for a focal origin in specific regions of the somatosensory cortex (Meeren et al., 2002; Polack et al., 2007; Zheng et al., 2012; McCafferty et al., 2018). | 0 | 37275776 |
Previous parts have also discussed that the X-inactivation may involve in the phenotype heterogeneity, and the skewed X-inactivation was probably related to unaffected heterozygous female carriers. | 0 | 36970538 |
However, the details on whether the new phenotypes and genotypes of the NPRL3 gene do exist and the information on the correlation between genotype and clinical phenotype in patients with NPRL3-related epilepsy have not been clarified. | 1 | 36937533 |
Several studies have indicated that elevated levels of S100β in the cerebrospinal fluid and temporal lobe of epilepsy patients may be attributed to increased production or release by dysfunctional astrocytes | 0 | 37833937 |
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