The Unit of Medical Genetics boats an outstanding experience in development and application of innovative protocols aimed at identifying the genetic causes of intellectual disabilities, Autism Spectrum Disorders, Epilepsy, Neuromuscular Diseases, as well as neurodegenerative disorders, genodermatoses neurosensory deafness. Array-CGH analysis (molecular karyotyping) and next-generation sequencing (NGS) are carried out by expert biologists and lab technicians with the aim of getting, in collaboration to clinicians, the most careful diagnosis of complex phenotypes. For neuromuscular diseases integrated and complete diagnostic tests (histopathological examination, biochemical analysis, molecular-genetic study of muscle and other biological samples) are performed. Furthermore, one of the field of interest of basic research regards the biochemical mechanisms responsible for brain dysfunctions in the Fragile-X syndrome and neurodegenerative diseases (Parkinson's disease, Huntington's Disease, Alzheimer's Disease) with particular regard to the interaction of drug targets and the therapeutic potential of endogenous neural stem cells in neuroinflammation and neuroprotection mechanisms. In addition, the Pharmacogenetics service has been recently established. It is an emerging branch of medical therapy, focused on the study of inherited genetic factors leading to individual differences in drug sensitivity.
The results of the research are periodically published in peer-reviewed journals. In order to offer an innovative genetic diagnosis service to a wider number of people, the Unit of Medical Genetics collaborates with national and international centres and is open to collaborations with local organizations and institutions.
Molecular biology techniques (Real-Time PCR) and direct sequencing are performed for the diagnosis of the following diseases:
Fragile X (FMR1); Gilbert's Syndrome (UGT1A); Senile dementia; Apolipoprotein E (ApoE); Genetic Thrombophilia (Factor V Leiden, Prothrombin, MTHFR), Narcolepsy (HLA-DQB1 System); Celiac disease (HLA-DQ2 / DQ8 System ); Pharmacogenetics Test (genetic polymorphisms of cytochrome P450 enzyme system).
Research lines are mainly addressed to the studies of the role of the proaptotic gene LDOG-1 and the anti-inflammatory interleukins IL4 and IL13 genes in individuals with Parkinson's disease.
Genetic Diagnosis division
Diagnostics: molecular investigations based on array-CGH + SNP technology for the study and diagnosis of genetic diseases. Analysis of the following genes: L1CAM (MIM * 308840), MECP2 (MIM * 300005), CDKL5 (MIM * 300203), ATRX (MIM * 300032), RSK2 (MIM * 300075), PTEN (OMIM +601728). Analysis of genes involved in the pathogenesis of hereditary spastic paraplegia in NGS using custom panel.
Research is focused on the study of infantile epileptic encephalopathy using next generation sequencing, and on 180K CGH + SNP arrays as a diagnostic tool in neurodevelopmental disorders.
Molecular Genetics division
In recent years, the extraordinary scientific progress achieved in the field of genomics and biotechnology have laid the foundation for a better understanding of the information contained in DNA. At Oasi’s Laboratory of Molecular Genetics tests are carried out by means of state-of-the-art equipment, including sequencing (Next Generation Sequencing, NGS) and through a wide list of genetic testing (more than 100 hereditary genetic diseases) which are among the most comprehensive at regional and national level in the field of intellectual disabilities and neurodegenerative disorders.
Molecular tests are available for the following diseases: leukoencephalopathies, epilepsies, developmental diseases (RASOPATHIES), ataxias, atrophies, genodermatosEs, neurosensory deafness, phenylketonuria, ichthyosis, Alzheimer's disease, Darier's disease, neurofibromatosis, Legius syndrome, Parkinson’s disease, X-linked intellectual disabilities, Prader Willi/Angelman syndromes, DiGeorge syndrome, Rubinstein-Taybi syndrome, Smith-Magenis syndrome, Williams syndrome, sensorineural deafness, Thrombophilia.
The Research activities carried out at Unit of Medical Genetics are mainly related to autism, intellectual disabilities and neurodegenerative disorders thanks to highly-specialized research groups (Molecular Biologists, Clinicians, Medical Geneticians and Consultants) and in collaboration with national and international organizations, healthcare institutions and research centers.
The results of the research are periodically published in peer-reviewed journals.
In vivo and in vitro studies on the biochemical mechanisms responsible for brain dysfunction in the Fragile-X syndrome carried out on animal model of wild type and knockout mice for the FMR gene. Receptor Stimulation study in neuronal and astrocytes cultures and brain tissue. Pharmacological treatment, and cytotoxicity studies on syndrome associated with ID. Study of protein expression with western blotting method, immunohistochemistry and microscopy in animal models of syndromes associated with ID.
The research activity of the laboratory of Neuropharmacology is part of the research line related to brain aging process, having as main target the study of elderly vulnerability to neurodegenerative diseases, of the mechanisms responsible for the loss of brain self-repair capacity due to ageing process and genetic and environmental factors in order to identify early signals, target genes and transduction mechanisms involved in neuronal death in translational models of human diseases. These studies focus on the characterization of the mechanisms regulating neurogenesis in the adult brain and aging, with the aim of activating the endogenous processes of brain self-repair with a pharmacological targeting, and synergies between cell therapies and biotechnological drugs.
In particular, we are studying the neurostem response in experimental models of Parkinson's disease, Huntington's disease and Alzheimer's disease. Particular attention is given to neuroinflammatory processes of astro- and microglial brain compartments, which determine a progressive increase in neural stem cells vulnerability along with the screening of innovative drugs. The research include experiments on "in vitro" isolated cells and in preclinical experimental models of neurodegenerative diseases, in vivo, where the neuroprotective and/or re-generative effects are monitored.
Clinical Neuropathology division
The laboratory of Clinical neuropathology deals with the clinical and research activities of neuromuscular diseases.
In addition, activities are focused on the study of muscle biopsy with histological and histoenzymatic examination, immunohistochemistry testing, western-blot, biochemical dosage of respiratory chain enzymes, culture of myoblasts and fibroblasts, molecular genetic investigations for mitochondrial diseases, X-linkeddystrophinopathies, for congenital muscular dystrophies, laminopathies and neuroaxonal dystrophies.
The genes studied are: mtDNA with search for point mutations, rearrangements or total sequencing, dystrophin, PDHA1, SDHA, POLG1, POLG2, TWINKLE, ANT1, OPA1, APTX, PANK2, PLA2G6, TAZ, POMT1, POMT2, POMTGnt1, LARGE, FKRP, FKTN, GLA , RODGI, LMNA, BANF1.
List of services
Dr. Antonino Castellano Chiodo
Research collaborators (under Agreement)
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