Search

Your search keyword '"MESH : Mutation"' showing total 2 results
Start Over Descriptor "MESH : Mutation" Publisher springer science and business media llc
2 results on '"MESH : Mutation"'

1. A quality control program for mutation detection in KIT and PDGFRA in gastrointestinal stromal tumours

Author

Fabienne Escande, Jean Michel Coindre, Silvana Pilotti, Sébastien Forget, Paolo Dei Tos, Pierre Paul Bringuier, Maria Debiec-Rychter, Elena Tamborini, David Gonzalez, Nicolas Faur, L Morzuch, Isabelle Hostein, Louisa Toffolati, Sylvianne Olschwang, Jean-François Emile, Département de pathologie, Institut Bergonié - CRLCC Bordeaux, university of leuven, Department of Human Genetics, Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CA foncello Hospital, Department of pathology, Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Laboratoire de Physique des Lasers ( LPL ), Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut Galilée-Centre National de la Recherche Scientifique ( CNRS ), biology and pathological laboratory, Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Service de Pathologie, Institut Bergonié, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, UNICANCER, Radboud University Medical Center [Nijmegen], Centre de Recherche en Cancérologie de Marseille (CRCM / U891 Inserm), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Medical University of Gdańsk, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay

Subjects
Oncology, Receptor, Platelet-Derived Growth Factor alpha, MESH : Polymorphism, Genetic, MESH: Receptor, Platelet-Derived Growth Factor alpha, DNA Mutational Analysis, MESH: Quality Control, MESH : Genotype, medicine.disease_cause, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, MESH : Exons, 0302 clinical medicine, Surgical oncology, Genotype, MESH: DNA Mutational Analysis, 0303 health sciences, Mutation, MESH : Gastrointestinal Stromal Tumors, GiST, Gastroenterology, MESH : Quality Control, DNA, Neoplasm, Exons, 3. Good health, MESH: Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins c-kit, 030220 oncology & carcinogenesis, MESH: Laboratories, MESH : DNA, Neoplasm, MESH : Mutation, MESH: Gastrointestinal Stromal Tumors, Quality Control, medicine.medical_specialty, MESH: Mutation, Gastrointestinal Stromal Tumors, MESH: DNA, Neoplasm, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : DNA Mutational Analysis, PDGFRA, Biology, MESH : Laboratories, MESH : Proto-Oncogene Proteins c-kit, 03 medical and health sciences, Internal medicine, MESH: Polymorphism, Genetic, medicine, Humans, Genotyping, 030304 developmental biology, MESH: Humans, Polymorphism, Genetic, MESH : Humans, Hepatology, digestive system diseases, Immunology, MESH : Receptor, Platelet-Derived Growth Factor alpha, MESH: Exons, Laboratories
Abstract

International audience; BACKGROUND: Although most gastrointestinal stromal tumours (GIST) carry oncogenic mutations in KIT exons 9, 11, 13 and 17, or in platelet-derived growth factor receptor alpha (PDGFRA) exons 12, 14 and 18, around 10% of GIST are free of these mutations. Genotyping and accurate detection of KIT/PDGFRA mutations in GIST are becoming increasingly useful for clinicians in the management of the disease. METHOD: To evaluate and improve laboratory practice in GIST mutation detection, we developed a mutational screening quality control program. Eleven laboratories were enrolled in this program and 50 DNA samples were analysed, each of them by four different laboratories, giving 200 mutational reports. RESULTS: In total, eight mutations were not detected by at least one laboratory. One false positive result was reported in one sample. Thus, the mean global rate of error with clinical implication based on 200 reports was 4.5%. Concerning specific polymorphisms detection, the rate varied from 0 to 100%, depending on the laboratory. The way mutations were reported was very heterogeneous, and some errors were detected. CONCLUSION: This study demonstrated that such a program was necessary for laboratories to improve the quality of the analysis, because an error rate of 4.5% may have clinical consequences for the patient.

Published
2011
Full Text
View/download PDF

2. A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report

Author

Daniel Rabier, Silvia Napuri-Gouel, Annie Martin-Ponthieu, Michèle Brivet, Niels Gregersen, Monique Fontaine, Brage S. Andresen, Gilbert Briand, Karine Mention-Mulliez, Dries Dobbelaere, Christine Vianey-Saban, Ronald J.A. Wanders, Joseph Vamecq, Anne-Frédérique Dessein, David S. Millington, Laboratoire d'hormonologie, métabolisme-nutrition et oncologie (HMNO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Research Unit for Molecular Medicine, Aarhus University [Aarhus]-Institute of Clinical Medicine, Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de neurologie pédiatrique, branche épilepsie, Centre de référence des maladies métaboliques héréditaires, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'application de Spectrométrie de Masse (LASM), Université de Lille, Droit et Santé, Department of Paediatrics, Duke University Medical Center, Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Laboratory of Genetic Metabolic Diseases, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), This work was supported by grants from the French Ministère de la Santé (PHRC 2003R/ 1903) and FMO (Fédération des Maladies Orphelines)., Aarhus University [Aarhus] - Institute of Clinical Medicine, UNIVERSITY OF SOUTHERN DENMARK, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Hôpital Jeanne de Flandre [Lille] - Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Academic Medical Center [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA) - University of Amsterdam [Amsterdam] (UvA), Faculteit der Geneeskunde, BMC, Ed., Amsterdam Gastroenterology Endocrinology Metabolism, and Laboratory Genetic Metabolic Diseases

Subjects
Male, MESH: Oxidation-Reduction, MESH : Lymphocytes, lcsh:Medicine, MESH : Carnitine, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, Compound heterozygosity, Polymerase Chain Reaction, Acyl-CoA Dehydrogenase, 0302 clinical medicine, Genetics(clinical), MESH : Female, Pharmacology (medical), Lymphocytes, MESH : Acyl-CoA Dehydrogenase, MESH : Polymerase Chain Reaction, MESH : Fatty Acids, Cells, Cultured, Genetics (clinical), Skin, Medicine(all), Genetics, 0303 health sciences, MESH: Carnitine, Fatty Acids, MESH: Genetic Predisposition to Disease, MESH: Acyl-CoA Dehydrogenase, General Medicine, MESH : Adult, Pedigree, MESH: Fatty Acids, 3. Good health, Child, Preschool, Mutation (genetic algorithm), Female, MESH : Mutation, Oxidation-Reduction, ACADM Gene, MESH: Cells, Cultured, medicine.drug, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Pedigree, MESH : Male, Biology, 03 medical and health sciences, MESH : Deficiency Diseases, MESH: Skin, Carnitine, Internal medicine, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Skin, medicine, Humans, Genetic Predisposition to Disease, ACADM, 030304 developmental biology, MESH : Oxidation-Reduction, [SDV.GEN]Life Sciences [q-bio]/Genetics, Newborn screening, MESH: Humans, Research, lcsh:R, MESH : Humans, MESH: Child, Preschool, Acyl CoA dehydrogenase, MESH: Adult, MESH: Polymerase Chain Reaction, Fibroblasts, MCADD, medicine.disease, MESH: Male, Endocrinology, MESH: Deficiency Diseases, MESH: Fibroblasts, MESH : Pedigree, Mutation, biology.protein, MESH : Genetic Predisposition to Disease, MESH: Lymphocytes, Deficiency Diseases, MESH: Female, 030217 neurology & neurosurgery
Abstract

A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results