Valerio Conti
A5005057454- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Epilepsy research and treatment
- Advanced Breast Cancer Therapies
- Fetal and Pediatric Neurological Disorders
- Lung Cancer Research Studies
- Radiation Detection and Scintillator Technologies
- Radiation Therapy and Dosimetry
- HER2/EGFR in Cancer Research
- Neuroscience and Neuropharmacology Research
- Advanced Radiotherapy Techniques
- Cell Image Analysis Techniques
- Advanced Fluorescence Microscopy Techniques
- Single-cell and spatial transcriptomics
- Nuclear Physics and Applications
- Biometric Identification and Security
- Amino Acid Enzymes and Metabolism
- Ion channel regulation and function
- Optical Imaging and Spectroscopy Techniques
- Spectroscopy Techniques in Biomedical and Chemical Research
- Congenital heart defects research
- Ion Transport and Channel Regulation
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
Meyer Children's Hospital
2015-2024
University of Florence
2014-2023
Humanitas University
2020-2021
University of Bologna
2012-2020
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2020
Institute of Neurological Sciences
2020
ERN EpiCARE
2020
Fondazione IRCCS Istituto Neurologico Carlo Besta
2020
Policlinico S.Orsola-Malpighi
2020
University of Southern Denmark
2016
Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations development with shared neuropathologic features. These disorders are associated significant childhood morbidity mortality.To identify the underlying molecular cause FCD, diffuse megalencephaly.Patients or (mean age, 11.7 years; range, 2-32 years) were recruited from Pediatric Hospital A. Meyer, University Hong Kong, Seattle Children's Research Institute June 2012 to 2014....
Extensive mapping of neuronal connections in the central nervous system requires high-throughput um-scale imaging large volumes. In recent years, different approaches have been developed to overcome limitations due tissue light scattering. These methods are generally improve performance a specific modality, thus limiting comprehensive neuroanatomical exploration by multimodal optical techniques. Here, we introduce versatile brain clearing agent (2,2'-thiodiethanol; TDE) suitable for various...
PurposeTo define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 NPRL3 genes encoding GATOR1 complex, a negative regulator mTORC1 pathwayMethodsWe analyzed clinical genetic data 73 novel probands (familial sporadic) with epilepsy-related variants in GATOR1-encoding proposed new guidelines for interpretation variants.ResultsThe seizure phenotype consisted mostly focal seizures (e.g., hypermotor or frontal lobe 50%), mean age at onset 4.4 years, often...
Mosaicism is increasingly recognized as a cause of developmental disorders with the advent next-generation sequencing (NGS). Mosaic mutations PIK3CA have been associated widest spectrum phenotypes overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes amplicon in cohort 241 samples from 181 individuals brain and/or body overgrowth. identified 60 individuals. Several other (n = 12) were separately to...
<h3>Objective:</h3> To assess the prevalence of somatic <i>MTOR</i> mutations in focal cortical dysplasia (FCD) and germline a broad range epilepsies. <h3>Methods:</h3> We collected 20 blood-brain paired samples from patients with FCD searched for variants using deep-targeted gene panel sequencing. Germline were assessed French research cohort 93 probands epilepsies diagnostic Danish 245 Data sharing among collaborators allowed us to ascertain additional <i>MTOR</i>. <h3>Results:</h3>...
<h3>ABSTRACT</h3> <h3>Objective:</h3> To perform a clinical and genetic study of family with benign familial infantile seizures (BFIS) and, upon finding <i>PRRT2</i> gene mutation, to cohort probands similar phenotype. We extended the all available members find out whether mutations cosegregated additional symptoms. <h3>Methods:</h3> carried genealogic 3-generation 32 BFIS (11 families), convulsions paroxysmal choreoathetosis (ICCA) (9 BFIS/generalized epilepsy febrile plus (5 sporadic...
Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes brain overgrowth (megalencephaly) as segmental cortical dysplasia (such hemimegalencephaly, focal and polymicrogyria). AKT3 gene have been reported in a few individuals with malformations, to date. Therefore, our understanding regarding clinical molecular spectrum associated mutations this critical is limited, no clear genotype–phenotype correlations. We sought further delineate...
Abstract Background Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, diagnostic yields many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25–30%. This part because although entire genomes sequenced, analysis confined to silico gene panels or coding regions genome. Methods We undertook WGS on cohort 122 unrelated disease and their relatives (300 genomes) who had been pre-screened by...
Periventricular nodular heterotopia is caused by defective neuronal migration that results in heterotopic nodules lining the lateral ventricles. Mutations filamin A (FLNA) or ADP-ribosylation factor guanine nucleotide-exchange 2 (ARFGEF2) cause periventricular heterotopia, but most patients with this malformation do not have a known aetiology. Using comparative genomic hybridization, we identified 12 developmental brain abnormalities, variably combining corpus callosum dysgenesis,...
V-type proton (H+) ATPase (v-ATPase) is a multi-subunit pump that regulates pH homeostasis in all eukaryotic cells; neurons, v-ATPase plays additional and unique roles synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) ATP6V1A, encoding the A subunit of v-ATPase, four patients with developmental encephalopathy epilepsy. Early manifestations, observed patients, were delay febrile seizures, evolving...
Abstract Objectives Focal cortical dysplasia ( FCD ) is a major cause of drug‐resistant focal epilepsy in children, and the clinicopathological classification remains challenging issue daily practice. With recent progress DNA methylation–based human brain tumors we examined whether genomic methylation gene expression analysis can be used to also distinguish subtypes. Methods methylomes transcriptomes were generated from massive parallel sequencing 15 surgical specimens, matched with 5 6...
Single germline or somatic activating mutations of mammalian target rapamycin (mTOR) pathway genes are emerging as a major cause type II focal cortical dysplasia (FCD), hemimegalencephaly (HME) and tuberous sclerosis complex (TSC). A double-hit mechanism, based on primary mutation in one allele secondary hit affecting the other same gene small number cells, has been documented some patients with TSC FCD. In patient HME, severe intellectual disability, intractable seizures hypochromic skin...
Somatic and germline duplications or activating mutations of AKT3 have been reported in patients with hemimegalencephaly megalencephaly. We performed array comparative genomic hybridization on brain tissue blood 16 consecutive symptomatic epilepsy due to focal multilobar malformations cortical development who underwent surgical treatment epilepsy. One patient infantile spasms a dysplastic left frontal lobe harboured somatic trisomy the 1q21.1-q44 chromosomal region, encompassing gene, but...
With a complex and extremely high clinical genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described seems to have strong background. Macrocephaly also represents well-known endophenotype in subgroups individuals, which suggests pathogenic mechanisms accelerating brain growth early development predisposing the disorder. We attempted estimate...
Abstract Focal malformations of cortical development including focal dysplasia, hemimegalencephaly and megalencephaly, are a spectrum neurodevelopmental disorders associated with brain overgrowth, cellular architectural intractable epilepsy, autism intellectual disability. Importantly, dysplasia is the most common cause paediatric epilepsy. Gain loss function variants in PI3K-AKT-MTOR pathway have been identified this spectrum, variable levels mosaicism tissue distribution. In study, we...
Abstract Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in variety of cellular membranes that acts as an ATP-dependent proton pump and plays key role pH homeostasis intracellular signalling pathways. In humans, 22 autosomal genes encode for redundant set subunits allowing the composition diverse V-ATPase complexes with specific properties expression. Sixteen have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense...
Ohtahara syndrome, early infantile epileptic encephalopathy with a suppression burst EEG pattern, is an aetiologically heterogeneous condition starting in the first weeks or months of life intractable seizures and profound developmental disability. Using whole exome sequencing, we identified biallelic DMXL2 mutations three sibling pairs belonging to unrelated families. Siblings Family 1 were compound heterozygous for c.5135C>T (p.Ala1712Val) missense substitution c.4478C>G (p.Ser1493*)...
Myxoid glioneuronal tumor (MGT) is a benign neoplasm recently introduced in the World Health Organization (WHO) classification of central nervous system (CNS) tumors. MGTs are typically located septum pellucidum, foramen Monro or periventricular white matter lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, have been associated with specific...