Marco Crimi

Kaleidos SCS onlus

The exact physiopathology of ring chromosome 14 syndrome (RC14) (OMIM#616606) is currently unknown but it definitely does not rely only on the 14q deleted region, as the clinical severity does not correlate with the deletion size and gene content. The resulting clinical picture belongs to the large group of neurodevelopmental disorders associated w...

Patient advocacy organisations (PAOs) are increasingly involved in biomedical science and pharmaceutical research and development because of scientific advances and growing attention to rare diseases. They have traditionally focused on advocating for their patient community and providing practical support to individuals and families as they cope wi...

Genetic counselors are healthcare professionals who are trained in both medical genetics and counseling to help guide individuals through what is known about genetic predispositions toward a variety of diseases, how they are inherited, and what impact this information can have on them and their partners and families. The range and scope of practice...

Counseling after WES/WGS presents challenges for healthcare providers as the availability of consumer-driven is rapidly increasing. The present report uncovers an extremely rare homozygous nonsense mutation c. 1639C>T (p.Gln547Ter) in PRX gene of a patient with heterogeneous manifestation of Charcot-Marie-Tooth. Such studies can help to conduct gen...

Background: Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals. Main body: The aim of...

Background: Poland Syndrome (PS) is a rare congenital malformation involving functional and aesthetic impairments. Early diagnosis and timely therapeutic approaches play an important role in improving the quality of life of patients and kindred. This study aims to explore healthcare experiences of the diagnosis of patients affected by PS and to in...

Background Ring chromosome 14 syndrome is a rare chromosomal disorder characterized by early onset refractory epilepsy, intellectual disability, autism spectrum disorder and a number of diverse health issues. ResultsThe aim of this work is to provide recommendations for the diagnosis and management of persons affected by ring chromosome 14 syndrome...

The EuroBioBank (EBB) network (www.eurobiobank.org) is the first operating network of biobanks in Europe to provide human DNA, cell and tissue samples as a service to the scientific community conducting research on rare diseases (RDs). The EBB was established in 2001 to facilitate access to RD biospecimens and associated data; it obtained funding f...

Access to biological materials is a key prerequisite for scientific research in any medical field and in particular for research into rare diseases (RDs), for which obtaining high-quality samples and the related clinical data remains a major hurdle. RD biobanks play a pivotal role in making such materials and data available to the scientific commun...

Maternal inheritance of mtDNA is the rule in most animals, but the reasons for this pattern remain unclear. To investigate the consequence of overriding uniparental inheritance, we generated mice containing an admixture (heteroplasmy) of NZB and 129S6 mtDNAs in the presence of a congenic C57BL/6J nuclear background. Analysis of the segregation of t...

Unlabelled: Polymorphisms in the interleukin-28B (IL28B) region are associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked whether an association between I...

The impact of anti-TNF therapy on systemic immune responses in patients has not been clearly defined. Here, we examined Th1/Th2/Th17 cytokine expression, activation and proliferation of peripheral T cells from patients with psoriasis and inflammatory bowel disease before and during anti-TNF therapy. In parallel, we calculated the correlation with t...

Mitochondria are semi-autonomously reproductive organelles within eukaryotic cells carrying their own genetic material, called the mitochondrial genome (mtDNA). Until some years ago, mtDNA had primarily been used as a tool in population genetics. As scientists began associating mtDNA mutations with dozens of mysterious disorders, as well as the agi...

Mitochondrial deoxyribonucleic acid depletion syndromes are autosomal recessive disorders characterized by a reduction of the amount of mitochondrial deoxyribonucleic acid, which impairs the synthesis of respiratory chain complexes. Mutations in the deoxyguanosine kinase and polymerase gamma genes have been identified in hepatocerebral forms, where...

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an infantile autosomal-recessive motor neuron disease caused by mutations in the immunoglobulin micro-binding protein 2. We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase (ALDH) activity to modify disease pro...

Mitochondria are ubiquitous in eukaryotic cells where they generate much of the cellular energy by the process of oxidative phosphorylation (OXPHOS). The approximately 1500 genes of the mitochondrial genome are distributed between the cytoplasmic, maternally-inherited, mitochondrial DNA (mtDNA) which encodes 37 genes and the nuclear DNA (nDNA) whic...

A 45-year-old male patient had an episode of acute renal failure with myoglobinuria, myalgias, weakness, and markedly increased serum CK levels. Similar episodes had occurred in the past. Carnitine palmitoyl-transferase II (CPT II) deficiency was documented both biochemically and genetically. Interestingly, muscle biopsy also showed some ragged red...

Extremely variable clinic and genetic features characterize mitochondrial encephalomyopathy (MEM). Pathogenic mitochondrial DNA (mtDNA) defects can be divided into large-scale rearrangements and single point mutations. Clinical manifestations become evident when a threshold percentage of the total mtDNA is mutated. In some MEM, the "mutant load" in...

Converging evidence points to a pivotal role of vascular endothelial growth factor (VEGF) in neuronal protection and a lack of its activity in neurodegenerative disorders. To investigate this possible association, we screened the VEGF gene promoter for various well-known single-nucleotide polymorphisms in a series of 249 consecutively recruited Ita...

Dysferlin plays an essential role in the muscle repair machinery, and its deficiency is associated with limb-girdle muscular dystrophy type 2B and with two different distal myopathies (Miyoshi myopathy and distal anterior compartment myopathy). Our aims were to characterize the pattern of dysferlin expression during myogenic cell differentiation an...

We describe a new mitochondrial DNA mutation in a male infant who presented clinical and magnetic resonance imaging features of Leigh syndrome and died at the age of 9 mo. The patient's development was reportedly normal in the first months of life. At the age of 5 mo, he presented severe generalized hypotonia, nystagmus, and absent eye contact. Lab...

Mitochondrial encephalomyopathies are highly variable clinically and at the genetic level. In practice, when the mitochondrial DNA (mtDNA) of any mitochondrial-patient is sequenced, a very high number of variations are noted. The vast majority of these differences are simply polymorphisms, that is, non-pathologic, homoplasmic sequence variations; h...

Retinoic acid (RA), an active metabolite of vitamin A, is a natural morphogen involved in development and differentiation of the nervous system. To elucidate signaling mechanisms involved in RA-induced neuritogenesis, we used human neuroblastoma SH-SY5Y cells, an established in vitro model for studying RA action, to examine the role of extracellula...

The accumulation of multiple mitochondrial DNA (mtDNA) deletions in stable tissues is a distinctive feature of several autosomal disorders, characterized by Progressive External Ophthalmoplegia (PEO), ptosis, and proximal myopathy. At least three nuclear genes are responsible for these disorders: ANT1 and C10orf2 cause autosomal dominant PEO, while...

Mitochondrial (mt)DNA alterations cause cellular energy failure and respiratory chain dysfunction. Single large-scale rearrangements represent the most common mtDNA mutations and are responsible for very variable clinical manifestations. Here, we show an increased frequency of the A12308G substitution, a common polymorphism used to define the Europ...

The ageing process is associated with the accumulation of somatic mutations of mitochondrial DNA (mtDNA). The aged human skeletal muscle tissue presents a mosaic of fibers when stained histochemically for cytochrome c oxidase (COX) activity with a proportion of COX negative fibers. Given the potential relevance of any alteration in the mtDNA contro...

To better understand the still unknown pathologic mechanism involved in the accumulation of multiple mtDNA deletions in stable tissues. A large-scale screening of mtDNA molecules from skeletal muscle was performed in 14 patients with progressive external ophthalmoplegia (PEO) and 2 patients with mitochondrial neurogastrointestinal encephalomyopathy...

Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a methionine (M) for valine (V) substitution at codon 129 has been associated with cognitive impairment in elderly individuals. Down syndrome (DS) is associated with mental retardation and development of Alzheimer-like brain abnormalities. In the present study, we investigate...

A 13084 A->T missense mutation in the mitochondrial ND5 gene was identified in a 16-year-old boy affected with a progressive neurodegenerative disorder combining features of Leigh and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) syndromes. Muscle biopsy analysis revealed partial complex I deficiency. The mutatio...

We have identified a heteroplasmic G to A mutation at position 12,183 of the mitochondrial transfer RNA Histidine (tRNA(His)) gene in three related patients. These phenotypes varied according to mutation heteroplasmy: one had severe pigmentary retinopathy, neurosensorial deafness, testicular dysfunction, muscle hypotrophy, and ataxia; the other two...

Mitochondria are involved in cellular energy production via oxidative phosphorylation and this function may be damaged by any mutation in mitochondrial DNA (mtDNA). To identify novel mtDNA mutations, we have developed a program to systematically screen the entire mitochondrial genome in a large number of individuals with clinical and/or morphologic...

The progressive accumulation of mitochondrial DNA (mtDNA) alterations, ranging from single mutations to large-scale deletions, in both the normal ageing process and pathological conditions is a relevant phenomenon in terms of frequency and heteroplasmic degree. Recently, two point mutations (A189G and T408A) within the Displacement loop (D-loop) re...

We have demonstrated in the SH-SY5Y human neuroblastoma cell line that the antineoplastic drug paclitaxel induces apoptosis associated with the phosphorylation of c-raf and Bcl-2, thus causing Bcl-2 inactivation. In addition, we have observed the cleavage of caspase 7 and PARP, and the involvement of JNK/SAPK cascade. In this study, we investigated...

ABSTRACT Spinal muscular ,atrophy ,with respiratory distress type 1 (SMARD1) is an ,infantile autosomal recessive motor neuron disease, caused by mutations in the Immunoglobulin µ-binding protein 2 (IGHMBP2). Weinvestigated,the potential of a,spinal cord neural stem cell population isolated on the,basis of