A5020751804- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- ATP Synthase and ATPases Research
- Coenzyme Q10 studies and effects
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Photosynthetic Processes and Mechanisms
- RNA regulation and disease
- Retinal Development and Disorders
- Amyotrophic Lateral Sclerosis Research
- RNA modifications and cancer
- Structural Health Monitoring Techniques
- Autism Spectrum Disorder Research
- Acoustic Wave Phenomena Research
- Drug-Induced Ocular Toxicity
- Genomics and Rare Diseases
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Organic Chemistry Cycloaddition Reactions
- Genetic factors in colorectal cancer
- Psychological and Temporal Perspectives Research
- Peroxisome Proliferator-Activated Receptors
- Thyroid Cancer Diagnosis and Treatment
- Neurogenetic and Muscular Disorders Research
- BRCA gene mutations in cancer
Istituto delle Scienze Neurologiche di Bologna
2020-2025
Institute of Neurological Sciences
2023-2025
University of Bologna
2014-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2022-2023
Azienda USL di Bologna
2023
Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% patients, but we can neither predict nor understand non-responders. Idebenone is reduced by cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons respiratory complex III, bypassing affected LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers...
The endosomal sorting complex required for transport (ESCRT) machinery is essential membrane remodeling and autophagy it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. phenotypic included four severe developmental epileptic encephalopathy, massive reduction white...
Aims/Purpose: The genetic landscape of inherited optic neuropathies is continuously expanding and includes numerous nuclear DNA‐encoded genes or loci 1 , encompassing dominant, recessive, X‐linked inheritance patterns. Pathogenic variants in respiratory Complex I (CI) genes, typically are associated to severe early onset phenotypes, but have occasionally identified also syndromic atrophy. Therefore, we investigated CI identify pathogenic patients with atrophy who previously tested negative...
Aims/Purpose: This is an observational study to track the disease course of patients affected by Leber Hereditary Optic Neuropathy (LHON), regularly attending neurophthalmological clinic IRCCS ISNB (Bologna). Methods: To satisfy inclusion criteria, subjects needed a confirmed genetic diagnosis for 2 3 primary LHON mutations (m.11778G > A/MT‐ ND4 ; m.3460G ND1 ). There was no restriction on age, and could have received idebenone or any other treatment. Results: 397 from 137 families were...
Aims/Purpose: This is an observational study to track the disease course of patients affected by Leber Hereditary Optic Neuropathy (LHON), regularly attending neurophthalmological clinic IRCCS ISNB (Bologna). Methods: To satisfy inclusion criteria, subjects needed a confirmed genetic diagnosis for 2 3 primary LHON mutations (m.11778G > A/MT‐ ND4 ; m.3460G ND1 ). There was no restriction on age, and could have received idebenone or any other treatment. Results: 397 from 137 families were...
Background Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder characterised by complex I defect leading to sudden degeneration of retinal ganglion cells. Although typically associated with pathogenic variants in DNA, LHON was recently described patients carrying biallelic nuclear genes DNAJC30 , NDUFS2 and MCAT . part fatty acid synthesis (mtFAS), as also MECR, the trans-2-enoyl-CoA reductase. MECR mutations lead recessive childhood-onset syndromic dystonia, atrophy basal...
Many physiological processes in the human body follow a 24-h circadian rhythm controlled by clock system. Light, sensed retina, is predominant "zeitgeber" able to synchronize rhythms light-dark cycles. Circadian dysfunction and sleep disorders have been associated with aging neurodegenerative diseases including mild cognitive impairment (MCI) Alzheimer's disease (AD). In present study, we aimed at investigating genetic variability of genes AD patients compared healthy controls from Italy. We...
Abstract Papillary thyroid carcinoma tall cell variant (PTC‐TCV), a form of PTC regarded as an aggressive subtype, shares several morphologic features with oncocytic tumors. Pathogenic homoplasmic/highly heteroplasmic somatic mitochondrial DNA (mtDNA) mutations, usually affecting oxidative phosphorylation (OXPHOS) complex I subunits, are hallmarks cells. To clarify the relationship between PTC‐TCV and tumors, 17 16 non‐TCV controls (cPTC) were subjected to: (1) transmission electron...
Abstract CoenzymeQ10 is one of the main cellular antioxidants and an essential lipid involved in numerous cell reactions, such as energy production apoptosis modulation. A large number enzymes are CoQ10 biosynthesis. Mutations genes encoding for these cause a deficiency, characterized by neurological systemic symptoms. Here we describe two young sisters with sensorineural deafness followed optic atrophy, due to novel homozygous pathogenic variant PDSS1 . The visual system seems be mainly...
Autism spectrum disorder (ASD) is a clinically heterogeneous class of neurodevelopmental conditions with strong, albeit complex, genetic basis. The architecture ASD includes different models, from monogenic transmission at one end, to polygenic risk given by thousands common variants small effects the other end. mitochondrial DNA (mtDNA) was also proposed as modifier for ASD, mostly focusing on maternal mtDNA, since paternal mitogenome not transmitted offspring. We extensively studied...
The generation of inducible pluripotent stem cells (iPSCs) is a revolutionary technique allowing production patient-specific cell lines used for disease modeling, drug screening, and therapy. Integrity nuclear DNA (nDNA) mandatory to allow iPSCs utilization, while quality control mitochondrial (mtDNA) rarely included in the validation process. In this study, we performed mtDNA deep sequencing during transition from parental fibroblasts reprogrammed iPSC differentiated neuronal precursor...
Autism spectrum disorder (ASD) is characterized by a complex polygenic background, but with the unique feature of subset cases (~15%-30%) presenting rare large-effect variant. However, clinical interpretation in these often complicated incomplete penetrance, variable expressivity and different neurodevelopmental trajectories. NRXN1 intragenic deletions represent prototype such ASD-associated susceptibility variants. From chromosomal microarrays analysis 104 ASD individuals, we identified an...
gene encodes for Upstream Binding Transcription Factor, an essential protein RNA metabolism. A recurrent de novo variant (c.628G>A; p.Glu210Lys) has recently been associated with a childhood-onset neurodegenerative disorder characterized by motor and language regression, ataxia, dystonia, acquired microcephaly. In this study, we report the clinical, metabolic, molecular genetics neuroimaging findings histologic, histochemical, electron microscopy studies in muscle samples of 2 patients from...
Isolated complex I deficiency represents the most common mitochondrial respiratory chain defect involved in disorders. Among these, DNA (mtDNA) m.13513G>A pathogenic variant NADH dehydrogenase 5 subunit gene (MT-ND5) has been associated with heterogenous manifestations, including phenotypic overlaps of encephalomyopathy lactic acidosis and stroke-like episodes, Leigh syndrome, Leber's hereditary optic neuropathy (LHON). Interestingly, this specific mutation recently described patients...
Abstract Background Myoclonus, Epilepsy and Ragged-Red-Fibers (MERRF) is a mitochondrial encephalomyopathy due to heteroplasmic mutations in DNA (mtDNA) most frequently affecting the tRNA Lys gene at position m.8344A > G. Defective severely impairs protein synthesis respiratory chain when high percentage of mutant heteroplasmy crosses threshold for full-blown clinical phenotype. Therapy currently limited symptomatic management myoclonic epilepsy, supportive measures counteract muscle...
Idebenone is the only approved treatment for Leber's hereditary optic neuropathy (LHON). It promotes recovery of visual function in up to 50% patients, but, based on current knowledge, we can neither predict nor understand non‐responders. reduced by cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons respiratory complex III, bypassing affected LHON. We explored possibility that genetic variant NQO1 enzyme impact idebenone response. found two polymorphic variants...
Barboni, Piero MD; Battista, Marco Brotto, Luigi Nucci, Paolo Checchin, Lisa Bandello, Francesco Fiorini, Claudio PhD; Ormanbekova, Danara Carelli, Valerio MD, Cascavilla, Maria Lucia Caporali, Leonardo PhDEditor(s): Avery, Robert DO; Golnik, Karl C. Froment, Caroline Wang, An-Guor MD Author Information