Search results for "DNA Mutational Analysis"
showing 10 items of 237 documents
A Network Model for the Correlation between Epistasis and Genomic Complexity
2008
The study of genetic interactions (epistasis) is central to the understanding of genome organization and evolution. A general correlation between epistasis and genomic complexity has been recently shown, such that in simpler genomes epistasis is antagonistic on average (mutational effects tend to cancel each other out), whereas a transition towards synergistic epistasis occurs in more complex genomes (mutational effects strengthen each other). Here, we use a simple network model to identify basic features explaining this correlation. We show that, in small networks with multifunctional nodes, lack of redundancy, and absence of alternative pathways, epistasis is antagonistic on average. In c…
Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study
2017
Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major…
Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene diagnosed using next-generation sequencing.
2016
Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features.…
Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts
2020
International audience; Treatment with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand (PD-L1) can generate durable responses in various cancer types, but only in a subset of patients. The use of predictive biomarkers for response to PD-1/PD-L1 inhibitors is critical for patient selection. Expression of PD-L1 has demonstrated utility in patient selection. Tumour mutational burden (TMB) is an emerging biomarker for response to PD-1/PD-L1 inhibitors. The evaluation of this biomarker is based on the hypothesis that a high number of mutations in somatic exonic regions will lead to an increase in neoantigen production, which could then be recognised by…
Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)
2017
Background and aims: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationw…
Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease-Associated Colorectal Cancer.
2021
doi: 10.1053/j.gastro.2021.04.042 Background & Aims Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs. Methods Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue sam…
Clinical and molecular characterization of 112 single-center patients with Neurofibromatosis type 1.
2018
Abstract Background The aim of this retrospective study was to define clinical and molecular characteristics of a large sample of neurofibromatosis type 1 (NF1) patients, as well as to evaluate mutational spectrum and genotype-phenotype correlation. NF1 is a relatively common neurogenetic disorder (1:2500–1:3000 individuals). It is caused by mutations of the NF1 gene on chromosome 17ql1.2, with autosomal dominant pattern of inheritance and wide phenotypical variability. Café-au-lait spots (CALs), cutaneous and/or subcutaneous neurofibromas (CNFs/SCNFs), skinfold freckling, skeletal abnormalities, Lisch nodules of the iris and increased risk of learning and intellectual disabilities, as well…
Dynamic regulatory interaction between cytomegalovirus major tegument protein pp65 and protein kinase pUL97 in intracellular compartments, dense bodi…
2017
Human cytomegalovirus (HCMV) is a ubiquitous pathogen of considerable clinical importance. Understanding the processes that are important for viral replication is essential for the development of therapeutic strategies against HCMV infection. The HCMV-encoded protein kinase pUL97 is an important multifunctional regulator of viral replication. Several viral and cellular proteins are phosphorylated by pUL97. The phosphoprotein pp65 is one important substrate of pUL97. It is the most abundant tegument protein of HCMV virions, mediating the upload of other virion constituents and contributing to particle integrity. Further to that, it interferes with host innate immune defences, thereby enablin…
Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer
2017
Abstract: Introduction: The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required.Areas covered:…
Molecular, clinical and neuropsychological study in 31 patients with Kabuki syndrome and KMT2D mutations
2017
IF 3.326; International audience; Kabuki syndrome (KS-OMIM 147920) is a rare developmental disease characterized by the association of multiple congenital anomalies and intellectual disability. This study aimed to investigate intellectual performance in children with KS and link the performance to several clinical features and molecular data. We recruited 31 children with KMT2D mutations who were 6 to 16 years old. They all completed the Weschler Intelligence Scale for Children, fourth edition. We calculated all indexes: the Full Scale Intellectual Quotient (FSIQ), Verbal Comprehension Index (VCI), Perceptive Reasoning Index (PRI), Processing Speed Index (PSI), and Working Memory Index (WMI…