👤 M A Donati

Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69-8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69-8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57-8.79; p = 0.003) were associated with a significantly worse disease-free survival. Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma. Show less

The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high ( This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted. Show less

We present a 29-year-old man with visual failure since childhood, muscle weakness, subtle heart muscle hypertrophy, and seizures who was initially considered to be affected by a mitochondrial encephalomyopathy because of the multiple unspecific involvement of brain, muscle and retinal tissues. Only the muscle biopsy findings correctly guided the genetic investigations and the identification of an autophagic vacuolar myopathy due to a homozygous mutation in CLN3. We believe that information in autophagic muscle disorders should further alert clinicians to consider CLN3 in individuals with vacuolar myopathy, especially if they have visual and cardiac involvement. Show less

Carbamoyl Phosphate Synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder, potentially leading to lethal hyperammonemia. Based on the age of onset, there are two distinct phenotypes: neonatal and late form. The CPS1 enzyme, located in the mitochondrial matrix of hepatocytes and epithelial cells of intestinal mucosa, is encoded by the CPS1 gene. At present more than 220 clear-cut genetic lesions leading to CPS1D have been reported. As most of them are private mutations diagnosis is complicated. Here we report an overview of the main clinical findings and biochemical and molecular data of 13 CPS1D Italian patients. In two of them, one with the neonatal form and one with the late form, cadaveric auxiliary liver transplant was performed. Mutation analysis in these patients identified 17 genetic lesions, 9 of which were new confirming their "private" nature. Seven of the newly identified mutations were missense/nonsense changes. In order to study their protein level effects, we performed an in silico analysis whose results indicate that the amino acid substitutions occur at evolutionary conserved positions and affect residues necessary for enzyme stability or function. Show less

Carbamyl Phosphate Synthetase I deficiency (CPSID) is a rare autosomal recessive urea cycle disorder usually characterized by potentially lethal neonatal hyperammonemia. The large (5215 bp) CPS1-cDNA, expressed only in liver and epithelial cells of intestinal mucosa, has been cloned. Until now the CPS1 genomic organization was unknown. Taking advantage of the phylogenetic lineage between the CPS1 gene of Homo sapiens and Rattus norvegicus, we determined the intron-exon organization of the human CPS1 gene. Starting from the ATG codon, the CPS I gene is organized in 38 exons spanning from 50bp to 200 bp. We also report the molecular studies on an Italian patient affected by neonatal CPSD. Two novel genetic lesions (c.1370T>G and c.2429A>G) that lead to the novel amino acid substitutions V457G and Q810R, and the known N1406T polymorphism, were detected in the patient's CPS1 RNA and in genomic DNA isolated from peripheral blood lymphocytes. The characterization of the CPS1 genomic organization will allow the identification of the genetic lesions of CPSD patients, the detection of carriers, better genetic counseling and a more certain, less invasive method of prenatal diagnosis. Show less