A5090589968- Genomics and Rare Diseases
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- RNA modifications and cancer
- Neurological diseases and metabolism
- Botulinum Toxin and Related Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- RNA regulation and disease
- Glycogen Storage Diseases and Myoclonus
- Autism Spectrum Disorder Research
- Cellular transport and secretion
- Hereditary Neurological Disorders
- Porphyrin Metabolism and Disorders
- Genomic variations and chromosomal abnormalities
- Neurological Disease Mechanisms and Treatments
- Metabolism and Genetic Disorders
- Cancer-related gene regulation
- Ion channel regulation and function
- Lysosomal Storage Disorders Research
- Autophagy in Disease and Therapy
- Neurological Disorders and Treatments
- Blood disorders and treatments
- Chemical Reactions and Isotopes
Fondazione IRCCS Istituto Neurologico Carlo Besta
2014-2024
University of Milan
2014
Ospedale Maggiore
2014
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2014
Istituti Clinici di Perfezionamento
2014
Istituti di Ricovero e Cura a Carattere Scientifico
2014
Don Carlo Gnocchi Foundation
2014
University of Milano-Bicocca
2014
University of Pisa
2013
Moscow Research and Clinical Center for Neuropsychiatry
2011
Mutations in PARK2, encoding Parkin, cause an autosomal recessive form of juvenile Parkinson Disease (JPD). The aim the present study was to investigate impact PARK2 mutations on mitochondrial function and morphology human skin fibroblasts. We analyzed cells obtained from four patients clinically characterized by JPD, harboring PARK2. By quantitative PCR we found a reduction (<50%) transcript all but one; however Western Blot analysis demonstrated virtual absence Parkin protein mutant...
Abstract Background Childhood‐onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood‐onset dystonia. Objective To define the frequency mutations in a cohort dystonic patients aged <18 years at onset, associated clinical and radiological phenotype, natural history disease. Methods Whole‐exome sequencing or customized gene panels were used to screen 65 who had previously tested negative for all other known...
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder associated with brain iron accumulation. The MRI abnormality consists of T<sub>2</sub> hypointensity in the globus pallidus small hyperintensity its medial part, called "eye-of-the-tiger" sign. We report on 2 patients affected by PKAN, whom examination did not demonstrate sign early stages; typical abnormalities were detected only following examinations. Case 1 4-year-old boy first studied at age years for psychomotor...
Pallidal deep brain stimulation is an established treatment in dystonia. Available data on the effect DYT-THAP1 dystonia (also known as DYT6 dystonia) are scarce and long-term follow-up studies lacking. In this retrospective, multicenter case series of medical records such patients, clinical outcome pallidal dystonia, was evaluated. The Burke Fahn Marsden Dystonia Rating Scale served measure. Nine females 5 males were enrolled, with a median 4 years 10 months after implant. All benefited...
Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. Heterozygous variants in lysine methyltransferase 2B (KMT2B), encoding histone H3 methyltransferase, have been associated with childhood-onset, progressive complex form of dystonia (dystonia 28, DYT28). Since 2016, more than one hundred rare KMT2B reported, including frameshift, nonsense, splice...
Background Heterozygous mutations in the GBA gene, encoding lysosomal enzyme β-glucocerebrosidase (GCase), are most frequent genetic risk factor for Parkinson’s disease (PD). -related PD (GBA-PD) patients have higher of dementia and reduced survival than non-carriers. Preclinical studies one open-label trial humans demonstrated that chaperone ambroxol (ABX) increases GCase levels modulates α-synuclein blood cerebrospinal fluid (CSF). Methods analysis In this multicentre, double-blind,...
To test the hypothesis that adult-onset primary dystonia may be underlying etiology of tremulous patients with clinical diagnosis Parkinson disease (PD) but without evidence dopaminergic deficit at nigrostriatal SPECT imaging.We retrospectively reviewed and imaging data PD assessed our tertiary movement disorder clinic, who underwent dopamine transporter consecutively between 2002 2011. Molecular screening for DYT1, DYT5, DYT6, DYT11, DYT16 genes was performed in all cases met following...
We present a group of patients affected by paediatric onset genetic encephalopathy with cerebral calcification unknown aetiology studied Next Generation Sequencing (NGS) analyses. collected all clinical and radiological data. DNA samples were tested means customized gene panel including fifty-nine genes associated known diseases calcification. series fifty patients. All displayed complex heterogeneous phenotypes mostly developmental delay pyramidal signs less frequently movement disorder...
Abstract Background and purpose Mutations in DNAJB2 are associated with autosomal recessive hereditary motor neuropathies/ Charcot‐Marie‐Tooth disease type 2 (CMT2). We describe an Italian family CMT2 due to a homozygous mutation provide insight into the pathomechanisms. Methods Patients mutations were characterized clinically, electrophysiologically by means of skin biopsy. mRNA protein levels studied lymphoblastoid cells (LCLs) from patients controls. Results Three affected siblings found...
Neuronal ceroid lipofuscinoses (NCLs) are genetically heterogeneous neurodegenerative disorders, characterized by progressive cognitive and motor decline, epilepsy, visual impairment, shortened life-expectancy. CLN6-related NCLs include both late-infantile adult myoclonic form. We report a 21-year-old patient, with mild developmental delay, who developed occipital seizures at 14 years, subsequently cortical myoclonus, photosensitivity low higher frequencies. Overall, the picture suited...
Autosomal dominantly inherited mutations in the GTP cyclohydrolase 1 ( GCH1 ) gene are associated with dopamine-responsive dystonia (DRD), also known as DYT5 .1 Rare atypical presentations have been described,2 including adulthood Parkinson disease (PD) vivo evidence of nigrostriatal degeneration.3
Paroxysmal dyskinesia (PD) refers to a group of heterogeneous syndromes characterized by recurrent attacks dystonia and/or chorea, without loss consciousness.1 PD are classified triggers as paroxysmal kinesigenic (PKD), nonkinesigenic (PNKD), and exertion-induced (PED). An increasing number genes have been implicated in their pathogenesis.1 Although defects the PRRT2 gene main cause PKD (77%–93% familial; 21%–45% sporadic),2 TMEM151A variants recently identified both familial isolated...
ABSTRACT Background and Objective Early‐onset Parkinson's disease (EOPD) commonly recognizes a genetic basis; thus, patients with EOPD are often addressed to diagnostic testing based on next‐generation sequencing (NGS) of PD‐associated multigene panels. However, NGS interpretation can be challenging in setting, few studies have this issue so far. Methods We retrospectively collected data from 648 PD age at onset younger than 55 years who underwent minimal shared panel 15 PD‐related genes, as...
Abstract Background VPS16 pathogenic variants have been recently associated with inherited dystonia. Most patients affected by dominant VPS16‐related disease display early‐onset isolated dystonia prominent oromandibular, bulbar, cervical, and upper limb involvement, followed slowly progressive generalization. Cases We describe six newly reported dystonic carrying mutations displaying unusual phenotypic features in addition to dystonia, such as myoclonus, choreoathetosis, pharyngospasm...
Abstract PLA2G6 is the causative gene for a group of autosomal recessive neurodegenerative disorders known as -associated neurodegeneration (PLAN). We present case with early-onset parkinsonism, ataxia, cognitive decline, cerebellar atrophy, and brain iron accumulation. Sequencing coding regions identified only heterozygous nonsense variant, but mRNA analysis revealed presence an aberrant transcript isoform due to novel deep intronic variant (c.2035-274G > A) leading activation...