Search results for " multiple"
showing 10 items of 903 documents
Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient
2021
Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alc…
Skraban‐Deardorff syndrome: Six new cases of WDR 26 ‐related disease and expansion of the clinical phenotype
2021
International audience; Skraban-Deardorff syndrome (a disease related to variations in the WDR26 gene; OMIM #617616) was first described in a cohort of 15 individuals in 2017. The syndrome comprises intellectual deficiency, severe speech impairment, ataxic gait, seizures, mild hypotonia with feeding difficulties during infancy, and dysmorphic features. Here, we report on six novel heterozygous de novo pathogenic variants in WDR26 in six probands. The patients’ phenotypes were consistent with original publication. One patient displayed marked hypotonia with an abnormal muscle biopsy; this finding warrants further investigation. Gait must be closely monitored, in order to highlight any muscul…
Lipidomic profiling identifies signatures of metabolic risk
2020
Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…
“Better explanations” in multiple sclerosis diagnostic workup
2019
BackgroundThe exclusion of other diseases that can mimic multiple sclerosis (MS) is the cornerstone of current diagnostic criteria. However, data on the frequency of MS mimics in real life are incomplete.MethodsA total of 695 patients presenting with symptoms suggestive of MS in any of the 22 RIREMS centers underwent a detailed diagnostic workup, including a brain and spinal cord MRI scan, CSF and blood examinations, and a 3-year clinical and radiologic follow-up.FindingsA total of 667 patients completed the study. Alternative diagnoses were formulated in 163 (24.4%) cases, the most frequent being nonspecific neurologic symptoms in association with atypical MRI lesions of suspected vascular…
Epidemiology and clonality of carbapenem-resistant Acinetobacter baumannii from an intensive care unit in Palermo, Italy
2012
Abstract Background Multidrug-resistant Acinetobacter baumannii, initially considered as having a poor clinical relevance, is frequently isolated from infection cases in intensive care units. We describe the epidemiology of carbapenem resistant A. baumannii (CRAB) in a general ICU in Palermo, Italy, from October 2010 to March 2011. Findings 58 of 61 isolates exhibited MICs for meropenem or imipenem ≥16 mg/L. Forty-nine carried blaOXA-23 and two blaOXA-58 genes. Five subtype clusters were detected by rep-PCR. Clusters D and E included 10 isolates that tested negative for the carbapenem resistance genes. MLST attributed all isolates, but two, with sequence type (ST)2, whereas the two remainin…
Redefining the MED13L syndrome
2015
Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficu…
Frequency and characterization of DNA methylation defects in children born SGA
2012
Various genes located at imprinted loci and regulated by epigenetic mechanisms are involved in the control of growth and differentiation. The broad phenotypic variability of imprinting disorders suggests that individuals with inborn errors of imprinting might remain undetected among patients born small for gestational age (SGA). We evaluated quantitative DNA methylation analysis at differentially methylated regions (DMRs) of 10 imprinted loci (PLAGL1, IGF2R DMR2, GRB10, H19 DMR, IGF2, MEG3, NDN, SNRPN, NESP, NESPAS) by bisulphite pyrosequencing in 98 patients born SGA and 50 controls. For IGF2R DMR2, methylation patterns of additional 47 parent pairs and one mother (95 individuals) of patie…
Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Reg…
2018
Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by “Federico II” Un…
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurologi…
2019
Abstract KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the …
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study.
2018
© 2018 The Authors.