Diego Lopergolo
A5078076094- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Autism Spectrum Disorder Research
- Peripheral Neuropathies and Disorders
- Hereditary Neurological Disorders
- Muscle Physiology and Disorders
- Cerebrovascular and genetic disorders
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Myasthenia Gravis and Thymoma
- CRISPR and Genetic Engineering
- Neurological diseases and metabolism
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Botulinum Toxin and Related Neurological Disorders
- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- BRCA gene mutations in cancer
- Single-cell and spatial transcriptomics
- Metalloenzymes and iron-sulfur proteins
- Nuclear Structure and Function
- Epilepsy research and treatment
- Gastrointestinal Tumor Research and Treatment
- Pain Mechanisms and Treatments
University of Siena
2018-2025
Azienda Ospedaliera Universitaria Senese
2018-2025
Fondazione Stella Maris
2022-2024
University of Verona
2024
Istituti di Ricovero e Cura a Carattere Scientifico
2023-2024
Center for Neurosciences
2023
University of Florence
2022
Agostino Gemelli University Polyclinic
2018
Sapienza University of Rome
2014-2016
Significance Amyotrophic lateral sclerosis (ALS) is a fatal disease leading to motor neuron degeneration and progressive paralysis. Other studies have revealed defects in skeletal muscle even the absence of anomalies, focusing on acetylcholine receptors (AChRs) supporting so-called “dying-back” hypothesis. Our results indicate that endocannabinoid palmitoylethanolamide (PEA) reduces rundown AChRs currents ALS can clinically improve patients’ pulmonary function. This study strengthens...
Summary We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies disruptive variants in individuals ascertained for severe neurodevelopmental delay, while 53 ASD; comparing ASD cases mutations groups reveals phenotypic differences....
The SLC12 gene family consists of SLC12A1-SLC12A9, encoding electroneutral cation-coupled chloride co-transporters. SCL12A2 has been shown to play a role in corticogenesis and therefore represents strong candidate neurodevelopmental disorder gene. Through trio exome sequencing we identified de novo mutations SLC12A2 six children with disorders. All had developmental delay or intellectual disability ranging from mild severe. Two sensorineural deafness. We also variants three individuals...
Abstract KCNN2 encodes the small conductance calcium-activated potassium channel 2 (SK2). Rodent models with spontaneous Kcnn2 mutations show abnormal gait and locomotor activity, tremor memory deficits, but human disorders related to variants are largely unknown. Using exome sequencing, we identified a de novo frameshift deletion in patient learning disabilities, cerebellar ataxia white matter abnormalities on brain MRI. This discovery prompted us collect data from nine additional patients...
Abstract KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context European collaborative study, we collected largest cohort KBGS patients (49). A combined array- based Comparative Genomic Hybridization next generation sequencing (NGS) approach investigated both genomic Copy...
Background/Objectives: Schuurs-Hoeijmakers syndrome (SHMS), also known as PACS1 neurodevelopmental disorder, is a rare condition characterized by intellectual disability, distinctive craniofacial abnormalities, and congenital malformations. SHMS has already been associated with variants in the gene 63 patients. In this study, we describe 10 new Italian patients all harboring common de novo p.(Arg203Trp) variant. Methods: The studied were evaluated clinical geneticists child neurologists...
The mitochondrial DNA (mtDNA) genes MT-ATP6 and MT-ATP8 encode for subunits α 8 (A6L) of the adenosine triphosphate synthase complex. Pathogenetic variants in MT-ATP6/8 cause incurable syndromes encompassing a wide spectrum clinical features including ataxia, motor language developmental delay, deafness, retinitis pigmentosa, Leigh pattern brain MRI. Typically, higher levels mtDNA lead to more severe symptomatology although even individuals with similar mutational loads exhibit high...
We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies disruptive variants in individuals ascertained for severe neurodevelopmental delay, while 53 ASD; comparing ASD cases mutations groups reveals phenotypic differences....
Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of neurodegenerative disorders affecting primarily the cerebellum and/or its afferent tracts, often accompanied by damage other neurological or extra-neurological systems. Due to overlap clinical presentation among ARCAs and variety hereditary, acquired, reversible etiologies that can determine dysfunction, differential diagnosis is challenging, but also urgent considering ongoing development promising target therapies....
Objective: To identify novel biomarkers as an alternative diagnostic tool for limb girdle muscular dystrophy (LGMD). Background: LGMD encompasses a group of dystrophies characterized by proximal muscles weakness, elevated CK levels and dystrophic findings on muscle biopsy. Heterozygous CAPN3 mutations are associated with autosomal dominant LGMD-4, while biallelic can cause recessive LGMD-1. Diagnosis is currently often based invasive methods requiring biopsy or blood tests. In most cases...
The diagnostic process for myofibrillar myopathies (MFM) and distal (DM) is particularly complex because of the large number causative genes, existence still molecularly undefined disease entities, overlapping features between 2 categories. This study aimed to characterize a cohort patients affected by MFM DM identify most important prognostic aspects these diseases.
Hereditary Breast and Ovarian Cancer (HBOC) syndrome is a condition in which the risk of breast ovarian cancer higher than general population. The prevalent pathogenesis attributable to inactivating variants
Thanks to advances in gene sequencing, RYR1-related myopathy (RYR1-RM) is now known manifest itself vastly heterogeneous forms, whose clinical interpretation is, therefore, highly challenging. We set out develop a novel unsupervised cluster analysis method large patient population. The objective was analyze the main characteristics identify distinctive features of RYR1-RM and, thus, offer more precise genotype–phenotype correlations group potentially life-threatening disorders. studied 600...
Abstract Background The development of e-health technologies for teleconsultation and exchange knowledge is one the core purposes European Reference Networks (ERNs), including ERN EURO-NMD rare neuromuscular diseases. Within ERNs, Clinical Patient Management System (CPMS) a web-based platform that seeks to boost active collaboration within across network, implementing data sharing. Through CPMS, it possible both discuss patient cases make patients’ available registries databases in secure...
IQSEC2 mutations are associated with IQSEC2-related intellectual disability (ID). Phenotypic spectrum has been better defined in the last few years by increasing number of reported cases although genotype-phenotype relationship for remains overall complex. As ID a wide phenotypic diversity described Rett syndrome (RTT). Several patients harboring present clinical symptoms similar to RTT and some meet most criteria classic RTT. With aim establishing correlation, we collected data 16 point (15...
DROSHA encodes a ribonuclease that is subunit of the Microprocessor complex and involved in first step microRNA (miRNA) biogenesis. To date, has not yet been associated with Mendelian disease. Here, we describe two individuals profound intellectual disability, epilepsy, white matter atrophy, microcephaly dysmorphic features, who carry damaging de novo heterozygous variants DROSHA. constrained for missense moderately intolerant to loss-of-function (o/e = 0.24). The loss fruit fly ortholog...
Abstract Objective The postsynaptic density protein of excitatory neurons PSD‐95 is encoded by discs large MAGUK scaffold 4 ( DLG4 ), de novo pathogenic variants which lead to ‐related synaptopathy. major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy present in 50% the individuals, it has not been investigated detail. We describe here phenotypic spectrum associated comorbidities...
NOTCH3 encodes a transmembrane receptor critical for vascular smooth muscle cell function. variants are the leading cause of hereditary cerebral small vessel disease (SVD). While monoallelic cysteine-involving missense in well-studied autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), patients biallelic extremely rare not well characterised.