Electrophysiological characterization of a CaV3.1 calcium channel mutation linked to trigeminal neuralgia

Pflügers Archiv - European Journal of Physiology, Journal Year: 2023, Volume and Issue: 475(6), P. 711 - 718

Published: April 3, 2023

Language: Английский

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Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

STAR Protocols, Journal Year: 2021, Volume and Issue: 2(1), P. 100383 - 100383

Published: March 1, 2021

Here, we present a protocol to analyze de novo genetic variants derived from the whole-exome sequencing (WES) of proband-parent trios. We provide stepwise instructions for using existing pipelines call mutations (DNMs) and determine whether observed number such is enriched relative expected number. This may be extended any human disease trio-based cohort. Cohort size limiting determinant discovery high-confidence pathogenic DNMs. For complete details on use execution this protocol, please refer Dong et al. (2020).

Language: Английский

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Trigeminal Neuralgia as a Primary Demyelinating Disease: Potential Multimodal Evidence and Remaining Controversies

Journal of Pain, Journal Year: 2023, Volume and Issue: 25(2), P. 302 - 311

Published: Aug. 27, 2023

Language: Английский

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Role of TRAK1 variants in epilepsy: genotype–phenotype analysis in a pediatric case of epilepsy with developmental disorder

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Feb. 12, 2024

Purpose The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. aim of this study was investigate the genotype–phenotype -associated epilepsy. Methods Trio-based whole-exome sequencing performed on a cohort 98 patients with epilepsy unknown etiologies. Protein modeling VarCards database were used predict damaging effects variants. Detailed neurological phenotypes all having variants analyzed assess correlations. Results A novel compound heterozygous variant comprising c.835C > T, p.Arg279Cys c.2560A C, p.Lys854Gln identified in one pediatric patient. analyses revealed that damaging. patient received diagnosis early infantile epileptic spasms developmental disorder; he became seizure-free through valproate adrenocorticotropic hormone treatment. Further results for six 12 indicated biallelic (including homozygous or variants) associated disorders. Among these patients, eight (67%) had seven (58%) intractable anti-seizure medicines. Moreover, experienced refractory status epilepticus, which (88%) died life. To our knowledge, first reported case caused by Conclusion Biallelic can cause In seizures progress suggesting high risk poor outcomes requirement

Language: Английский

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Emerging Psychotropic Drug for the Treatment of Trigeminal Pain: Salvinorin A

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1619 - 1619

Published: Nov. 30, 2024

Trigeminal neuralgia (TN) is chronic pain caused by damage to the somatosensorial system on trigeminal nerve or its branches, which involves peripheral and central dysfunction pathways. triggers disruptive in regions of face, including within around mouth. Besides clinical experiences, translating language suffering into scientific terminology presents substantial challenges. Due complex multifactorial pathophysiology underlying pain, elucidating social impact significant difficulties. Carbamazepine oxcarbazepine are first-line treatments for TN, achieving approximately 50% reduction 60–70% treated patients. However, their efficacy often limited common side effects, such as dizziness, vertigo, nausea, seizures, cognitive symptoms. In some cases, patients experience severe myelosuppression, hyponatremia, hormonal imbalances, liver toxicity, suicidal ideation, teratogenicity, other adverse reactions. Given these limitations, search new painkiller candidates continues. Hence, we focused this review salvinorin A (SalA), a natural agonist κ-opioid receptors (KORs), demonstrated anti-nociceptive, anti-inflammatory, anti-neuropathic properties various experimental models spinal sensory system. Furthermore, preclinical evidence indicates that SalA does not induce dependence demonstrates favorable toxicological safety profile comparison with currently marketed opioid drugs. We propose Salvinorin promising candidate treating neuralgia, offering potential reduced effects.

Language: Английский

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Familial occurrence of classical and idiopathic trigeminal neuralgia

Journal of the Neurological Sciences, Journal Year: 2021, Volume and Issue: 434, P. 120101 - 120101

Published: Dec. 22, 2021

Trigeminal neuralgia (TN) is a severe facial pain disease with unknown pathogenesis. It has been thought that the familial form of TN rare prevalence about 1–2% among affected individuals, but emerging evidence suggests role genetic factors. This study examined occurrence patients classical or idiopathic TN. Patients recruited from hospital registry received an informed consent questionnaire, and individuals reporting other family members underwent structured phone-interview. For members, type TN, available clinical, imaging, management results patient records were studied. Pedigrees for all families established. included 268 either The was present in 41/268 (15.3%) patients, is, 37/244 (15.2%) 4/24 (16.7%) Total 38 identified, two 32/38 (84.2%), three 5/38 (13.2%) four 1/38 (2.6%) families. Comparing 41 cases 227 sporadic showed significantly earlier onset higher right-sided cases, while there no difference gender distribution, arterial hypertension trigeminal branch involved. Among more frequent than traditionally assumed.

Language: Английский

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Electrophysiological and computational analysis of Cav3.2 channel variants associated with familial trigeminal neuralgia

Molecular Brain, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 17, 2022

Abstract Trigeminal neuralgia (TN) is a rare form of chronic neuropathic pain characterized by spontaneous or elicited paroxysms electric shock-like stabbing in region the face. While most cases occur sporadic manner and are accompanied intracranial vascular compression trigeminal nerve root, alteration ion channels has emerged as potential exacerbating factor. Recently, whole exome sequencing analysis familial TN patients identified 19 variants gene CACNA1H encoding for Ca v 3.2T-type calcium channels. An initial 4 these pointed to pathogenic role. In this study, we assessed electrophysiological properties 13 additional TN-associated 3.2 expressed tsA-201 cells. Our data indicate that 6 out analyzed display their gating evidenced hyperpolarizing shift voltage dependence activation and/or inactivation resulting an enhanced window current supported variant recovery from inactivation. Simulation neuronal electrical membrane using computational model reticular thalamic neuron suggests could enhance excitability. Altogether, present study adds notion channel polymorphisms contribute etiology some further support role

Language: Английский

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GABRG1 variant as a potential novel cause of epileptic encephalopathy, hypotonia, and global developmental delay

American Journal of Medical Genetics Part A, Journal Year: 2022, Volume and Issue: 188(12), P. 3546 - 3549

Published: Sept. 19, 2022

Epileptic encephalopathies (EEs) are severe brain disorders with excessive ictal (seizure) and interictal (electrographic epileptiform discharges) activity in developing which may result progressive cognitive neuropsychological deterioration. In contrast to regular epilepsy where the treatment goal is prevent seizure (ictal) recurrence, patients EE treat both as well further progression. With introduction of genetic sequencing technologies over past 20 years, there growing recognition basis EE, majority due monogenic causes. Monogenic etiologies include pathogenic variants γ-aminobutyric acid type A receptor (GABA-A) encoding gene family. We present a 2-year-old patient hypotonia, global developmental delays. Clinical trio exome showed novel, de novo variant GABRG1. GABRG1 encodes γ1 subunit GABA-A receptor. To date, has not been an association This predicted be damaging protein structure function, patient's phenotype similar those other members

Language: Английский

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The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 13, 2023

Abstract Chronic pain is a common problem, with more than one-fifth of adult Americans reporting daily or on most days. It adversely affects quality life and imposes substantial personal economic costs. Efforts to treat chronic using opioids played central role in precipitating the opioid crisis. Despite an estimated heritability 25-50%, genetic architecture not well characterized, part because studies have largely been limited samples European ancestry. To help address this knowledge gap, we conducted cross-ancestry meta-analysis intensity 598,339 participants Million Veteran Program, which identified 125 independent loci, 82 are novel. Pain was genetically correlated other phenotypes, level substance use disorders, psychiatric traits, education level, cognitive traits. Integration GWAS findings functional genomics data shows enrichment for putatively causal genes (n = 142) proteins 14) expressed brain tissues, specifically GABAergic neurons. Drug repurposing analysis anticonvulsants, beta-blockers, calcium-channel blockers, among drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors experience highlight attractive targets.

Language: Английский

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The genetic architecture of pain intensity in a sample of 598,339 U.S. veterans

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: March 14, 2023

Abstract Chronic pain is a common problem, with more than one-fifth of adult Americans reporting daily or on most days. It adversely affects quality life and imposes substantial personal economic costs. Efforts to treat chronic using opioids played central role in precipitating the opioid crisis. Despite an estimated heritability 25–50%, genetic architecture not well characterized, part because studies have largely been limited samples European ancestry. To help address this knowledge gap, we conducted cross-ancestry meta-analysis intensity 598,339 participants Million Veteran Program, which identified 125 independent loci, 82 are novel. Pain was genetically correlated other phenotypes, level substance use disorders, psychiatric traits, education level, cognitive traits. Integration GWAS findings functional genomics data shows enrichment for putatively causal genes (n = 142) proteins 14) expressed brain tissues, specifically GABAergic neurons. Drug repurposing analysis anticonvulsants, beta-blockers, calcium-channel blockers, among drug groups, as having potential analgesic effects. Our results provide insights into key molecular contributors experience highlight attractive targets.

Language: Английский

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