A5021427652- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Epilepsy research and treatment
- Ion Transport and Channel Regulation
- Nicotinic Acetylcholine Receptors Study
- Genetics and Neurodevelopmental Disorders
- Vitamin C and Antioxidants Research
- Receptor Mechanisms and Signaling
- Genomics and Rare Diseases
- Long-Term Effects of COVID-19
- MicroRNA in disease regulation
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Extracellular vesicles in disease
- Neurogenetic and Muscular Disorders Research
- Ion Channels and Receptors
- Hereditary Neurological Disorders
- Fungal Plant Pathogen Control
- Neuroscience of respiration and sleep
- COVID-19 Clinical Research Studies
- Ocular Disorders and Treatments
- Muscle Physiology and Disorders
- Muscle and Compartmental Disorders
University of Naples Federico II
2016-2025
University of Chicago
2009-2013
University of Molise
2008-2013
University of the Basque Country
2013
Consejo Superior de Investigaciones Científicas
2013
Tunis El Manar University
2013
Institut Pasteur de Tunis
2013
Bambino Gesù Children's Hospital
2011-2012
Istituti di Ricovero e Cura a Carattere Scientifico
2011-2012
Universidad de la República
2010
Mutations in K v 7.2 ( KCNQ2 ) and 7.3 KCNQ3 genes, encoding for voltage-gated + channel subunits underlying the neuronal M-current, have been associated with a wide spectrum of early-onset epileptic disorders ranging from benign familial neonatal seizures to severe encephalopathies. The aim present work has investigate molecular mechanisms dysfunction caused by voltage-sensing domain mutations (R144Q, R201C, R201H) or (R230C) recently found patients encephalopathies and/or intellectual...
Mutations in the K V 7.2 gene encoding for voltage-dependent + channel subunits cause neonatal epilepsies with wide phenotypic heterogeneity. Two mutations affecting same positively charged residue S 4 domain of have been found children affected benign familial seizures (R213W mutation) or epileptic encephalopathy severe pharmacoresistant and neurocognitive delay, suppression-burst pattern at EEG, distinct neuroradiological features (R213Q mutation). To examine molecular basis this...
Variants in KCNQ2 encoding for Kv 7.2 neuronal K+ channel subunits lead to a spectrum of neonatal-onset epilepsies, ranging from self-limiting forms severe epileptic encephalopathy. Most pathogenic variants cause loss-of-function, whereas few increase activity (gain-of-function). We herein provide evidence new phenotypic and functional profile KCNQ2-related epilepsy: infantile spasms without prior neonatal seizures associated with gain-of-function gene variant. With use an international...
Objective Recent reports have described single individuals with neurodevelopmental disability (NDD) harboring heterozygous KCNQ3 de novo variants (DNVs). We sought to assess whether pathogenic in cause NDD and elucidate the associated phenotype molecular mechanisms. Methods Patients DNVs were identified through an international collaboration. Phenotypes characterized by clinical assessment, review of charts, electroencephalographic (EEG) recordings, parental interview. Functional...
Mutations in the KCNQ2 and KCNQ3 genes encoding for Kv 7.2 (KCNQ2; Q2) 7.3 (KCNQ3; Q3) voltage-dependent K(+) channel subunits, respectively, cause neonatal epilepsies with wide phenotypic heterogeneity. In addition to benign familial epilepsy (BFNE), mutations have been recently found families one or more family members a severe outcome, including drug-resistant seizures psychomotor retardation, electroencephalogram (EEG) suppression-burst pattern (Ohtahara syndrome), distinct...
AimsPlasmalemmal Kv7.1 (KCNQ1) channels are critical players in cardiac excitability; however, little is known on the functional role of additional Kv7 family members (Kv7.2-5) cells. In this work, expression, function, cellular and subcellular localization, potential cardioprotective against anoxic-ischaemic injury Kv7.4 have been investigated.
Summary Mutations in the KCNQ 2 gene encoding for voltage‐gated potassium channel subunits have been found patients affected with early onset epilepsies wide phenotypic heterogeneity, ranging from benign familial neonatal seizures ( BFNS ) to epileptic encephalopathy cognitive impairment, drug resistance, and characteristic electroencephalography EEG neuroradiologic features. By contrast, only few 3 mutations rarely described, mostly typical . We report clinical, genetic, functional data a...
Prior studies have revealed remarkable phenotypic heterogeneity in KCNQ2-related disorders, correlated with effects on biophysical features of heterologously expressed channels. Here, we assessed phenotypes and functional properties associated KCNQ2 missense variants R144W, R144Q, R144G. We also explored vitro blockade channels carrying R144Q mutant subunits by amitriptyline.Patients were identified using the RIKEE database through clinical collaborators. Phenotypes collected a standardized...
Gain-of-function (GoF) variants in KCNT1 channels cause severe, drug-resistant forms of epilepsy. Quinidine is a known blocker, but its clinical use limited due to severe drawbacks. To identify novel blockers, homology model human was built and used screen an in-house library compounds. Among the 20 molecules selected, five (
Kv7.2 and Kv7.3 subunits underlie the M-current, a neuronal K+ current characterized by an absolute functional requirement for phosphatidylinositol 4,5-bisphosphate (PIP2). gene mutations cause early-onset neonatal seizures with heterogeneous clinical outcomes, ranging from self-limiting benign familial to severe epileptic encephalopathy (Kv7.2-EE). In this study, biochemical consequences prompted recurrent variant (R325G) found independently in four individuals forms of neonatal-onset EE...
Developmental and epileptic encephalopathies (DEEs) are neurodevelopmental diseases characterized by refractory epilepsy, distinct electroencephalographic neuroradiological features, various degrees of developmental delay. Mutations in KCNQ2, KCNQ3, and, more rarely, KCNQ5 genes encoding voltage-gated potassium channel subunits variably contributing to excitability control specific neuronal populations at stages have been associated DEEs. In the present work, clinical features two DEE...
Abstract Voltage-gated, potassium-selective K V 7.4 channels are expressed in the inner ear and crucial for hair-cell function survival. Loss-of-function variants of KCNQ4 , gene encoding 7.4-channel subunits, cause non-syndromic progressive hearing loss (DFNA2). opening requires a voltage-dependent conformational change (activation) charged voltage-sensor domains (VSDs), its transduction to pore. Previously, fast charge displacement was reported during VSD activation at negative potentials,...
The Ciona intestinalis voltage sensor–containing phosphatase (Ci-VSP) shares high homology with the phosphatidylinositol enzyme known as PTEN (phosphatase and tensin homologue deleted on chromosome 10). We have taken advantage of similarity between these proteins to inquire about coupling sensing domains in Ci-VSP. Recently, it was shown that four basic residues (R11, K13, R14, R15) are critical for its binding onto membrane, required catalytic activity. Ci-VSP has three PTEN. Here, we show...
Significance E1 and Q1 protein subunits assemble to form I Kslow channels in the heart ear. Inherited mutations either subunit that decrease level or alter function can cause life-threatening cardiac arrhythmias deafness. The mechanism by which slows channel opening has been subject of active debate. Here, we use gating current measurements simultaneous recordings ionic currents changes fluorescence a probe on voltage sensors demonstrate movement manner is both necessary sufficient determine...
Abstract Objective Heterozygous variants in KCNQ2 or, more rarely, KCNQ3 genes are responsible for early‐onset developmental/epileptic disorders characterized by heterogeneous clinical presentation and course, genetic transmission, prognosis. While familial forms mostly include benign epilepsies with seizures starting the neonatal or early‐infantile period, de novo have been described sporadic cases of encephalopathy (EOEE) pharmacoresistant seizures, various age‐related pathological EEG...