Search results for " Mutation"
showing 10 items of 1212 documents
Cell expression of GDAP1 in the nervous system and pathogenesis of Charcot-Marie-Tooth type 4A disease
2007
Abstract Mutations in the mitochondrial protein GDAP1 are the cause of Charcot-Marie-Tooth type 4A disease (CMT4A), a severe form of peripheral neuropathy associated with either demyelinating, axonal or intermediate pheno-types. GDAP1 is located in the outer mitochondrial membrane and it seems that may be related with the mitochondrial network dynamics. We are interested to define cell expression in the nervous system and the effect of mutations in mitochondrial morphology and pathogenesis of the disease. We investigated GDAP1 expression in the nervous system and dorsal root ganglia (DRG) neuron cultures. GDAP1 is expressed in motor and sensory neurons of the spinal cord and other large neu…
The columnar gene vnd is required for tritocerebral neuromere formation during embryonic brain development of Drosophila.
2006
International audience; In Drosophila, evolutionarily conserved transcription factors are required for the specification of neural lineages along the anteroposterior and dorsoventral axes, such as Hox genes for anteroposterior and columnar genes for dorsoventral patterning. In this report, we analyse the role of the columnar patterning gene ventral nervous system defective (vnd) in embryonic brain development. Expression of vnd is observed in specific subsets of cells in all brain neuromeres. Loss-of-function analysis focussed on the tritocerebrum shows that inactivation of vnd results in regionalized axonal patterning defects, which are comparable with the brain phenotype caused by mutatio…
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
2015
G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an an…
Analysis of KRAS , NRAS , BRAF , PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients
2019
Little information is available on the clinical significance of cancer-related genes such as KRAS, NRAS, BRAF, PIK3CA and TP53 in nonmetastatic rectal cancer. We investigated mutations of these genes in a large prospective series of locally advanced rectal cancer (LARC) patients who were recruited into two phase II trials. Mutational analyses were performed with diagnostically validated methods including polymerase chain reaction, capillary electrophoresis single-strand conformational analysis, Sanger sequencing and next-generation sequencing. Associations between single or multiple gene mutations and clinicopathological characteristics and treatment outcomes were explored. Of these 269, 21…
Molecular Characterization of Relapsed Core-Binding Factor (CBF) Acute Myeloid Leukemia (AML)
2015
Abstract Background: CBF-AML is defined by recurrent genetic abnormalities which encompass t(8;21)(q22;q22), inv(16)(p13.1q22) or less frequently t(16;16)(p13.1;q22). Most frequent secondary chromosome aberrations in t(8;21) AML are del(9q) or loss of a sex chromosome, and in inv(16)/t(16;16) AML trisomy 22 or trisomy 8. At the molecular level mutations involving KIT, FLT3, or NRAS were identified as recurrent lesions in CBF-AML. However, the underlying genetic alterations which might trigger relapse in CBF-AML are not well delineated. Thus, the aim of our study was to characterize the clonal architecture of relapsed CBF-AML. Methods: We performed mutational profiling (KIT, FLT3-ITD, FLT3-T…
Marinesco-Sjögren syndrome caused by a new SIL1 frameshift mutation
2015
no abstract available
WIDENING THE SCOPE OF NEXT GENERATION SEQUENCING APPLICATIONS IN PEDIATRIC MEDICAL GENETICS
2018
Advances in DNA sequencing technologies through Next Generation Sequencing (NGS) approaches have enabled genome-wide discovery of chromosomal copy-number variants and single-nucleotide changes. NGS technologies are rapidly expanding our ability to identify and better define disease-causing mutations and genotype-phenotype correlation. Pediatric patients may particularly benefit from the introduction of these new technologies. Pediatricians must keep up with all these new skills, both in their residency programs as well as in their continuing medical education programs.
A nonsense mutation abrogates production of a functional enterotoxin A in Clostridium difficile toxinotype VIII strains of serogroups F and X.
1999
Clostridium difficile strains of toxinotype VIII from serogroups F and X are described as toxin B-positive, toxin A-negative (TcdB+ A-), although they harbour almost the entire tcdA gene. To identify the reason for the lack of TcdA detection, we analyzed catalytic and ligand domains of TcdA-1470 of the type strain of serogroup F, strain 1470. Using recombinant fragments, the C-terminal immunodominant ligand domain TcdA3-1470, spanning amino acid residues 1694-2711 (corresponding to VPI 10463 sequence), was detected in Western blots. Similar experiments using the recombinant N-terminal catalytic fragment TcdAc1-2-1470 (amino acid positions 1-544) failed. In addition, this fragment showed no …
Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis
2010
Background: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants.Methodology/Principal Findings: Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor mod…
Clinical, pathologic, and genetic features of massive soft tissue neurofibromas in a Sicilian patient
2008
Abstract CONTEXT: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X). OBJECTIVE: The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded. RESULTS: The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and rec…