Brassier A.,University of Paris Descartes |
Ottolenghi C.,University of Paris Descartes |
Boutron A.,pitaux universitaires Paris Sud |
Bertrand A.-M.,Besancon University Hospital Center |
And 10 more authors.
Molecular Genetics and Metabolism
The causes of Reye-like syndrome are not completely understood. Dihydrolipoamide dehydrogenase (DLD or E3) deficiency is a rare metabolic disorder causing neurological or liver impairment. Specific changes in the levels of urinary and plasma metabolites are the hallmark of the classical form of the disease. Here, we report a consanguineous family of Algerian origin with DLD deficiency presenting without suggestive clinical laboratory and anatomopathological findings. Two children died at birth from hepatic failure and three currently adult siblings had recurrent episodes of hepatic cytolysis associated with liver failure or Reye-like syndrome from infancy. Biochemical investigation (lactate, pyruvate, aminoacids in plasma, organic acids in urine) was normal. Histologic examination of liver and muscle showed mild lipid inclusions that were only visible by electron microscopy. The diagnosis of DLD deficiency was possible only after genome-wide linkage analysis, confirmed by a homozygous mutation (p.G229C) in the DLD gene, previously reported in patients with the same geographic origin. DLD and pyruvate dehydrogenase activities were respectively reduced to 25% and 70% in skin fibroblasts of patients and were unresponsive to riboflavin supplementation. In conclusion, this observation clearly supports the view that DLD deficiency should be considered in patients with Reye-like syndrome or liver failure even in the absence of suggestive biochemical findings, with the p.G229C mutation screening as a valuable test in the Arab patients because of its high frequency. It also highlights the usefulness of genome-wide linkage analysis for decisive diagnosis advance in inherited metabolic disorders. © 2012 Elsevier Inc. Source
Briend A.,Institute Of Recherche Pour Le Developpement |
Legrand P.,French National Institute for Agricultural Research |
Bocquet A.,University of Franche Comte |
Girardet J.-P.,University Pierre and Marie Curie |
And 11 more authors.
Archives de Pediatrie
Lipids are an important source of energy for young children and play a major role in the development and functioning of nervous tissue. Essential fatty acids and their long-chain derivatives also fulfill multiple metabolic functions and play a role in the regulation of numerous genes. The Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the French Agency for Food, Environmental and Occupational Health & Safety (Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail [ANSES]) have recently recommended a minimum daily intake in preformed long-chain polyunsaturated fatty acids (LC-PUFAs): arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Mother's milk remains the only reference, but the large variability in its DHA content does not guarantee that breastfed children receive an optimal DHA intake if the mother's intake is insufficient. For children fed with infant formulas, ARA and DHA intake is often below the recommended intake because only one-third of infant formulas available on the market in France are enriched in LC-PUFAs. For all children, linoleic acid (LA) intake is on average higher than the minimal recommended values. The consequences of these differences between intake and recommended values are uncertain. A cautious attitude is to come close to the current recommendations and to advise sufficient consumption of DHA in breastfeeding women. For bottle-fed children, infant formulas enriched in LC-PUFAs and with moderate levels of LA should be preferred. LC-PUFA-rich fish should be consumed during breastfeeding, and adapted vegetable oils when complementary foods are introduced. © 2014 Elsevier Masson SAS. Source
De Forges H.,University Pierre and Marie Curie |
De Forges H.,French National Center for Scientific Research |
Pilon A.,University Paris - Sud |
Pilon A.,pitaux Universitaires Est Parisien |
And 4 more authors.
Methods in Cell Biology
Microtubules display a very dynamic behavior, and the presence of the guanosine-triphosphate (GTP) cap at the plus ends of microtubules is essential to regulate microtubule dynamics. Dimitrov et al. (2008) showed that GTP-tubulin is present not only at the plus ends but also in discrete locations along the microtubule lattice. These GTP islands were proposed to contribute to rescue events. Studying the localization of GTP-tubulin in microtubules is essential to better comprehend some core aspects in the regulation of microtubule dynamics. In this chapter, we recapitulate essential tools to study the GTP-tubulin using the recombinant antibody MB11 from permeabilized cells to in vitro assays. © 2013 Elsevier Inc. Source
Cuny T.,University of Lorraine |
Chanson P.,University Paris - Sud |
Chanson P.,pitaux universitaires Paris Sud
Pituitary adenomas define slow growing tumors developing from anterior pituitary. Most often benign, their treatment and subsequent management are based on transphenoidal surgery and/or medical therapy, generally without difficulties in clinical practice. However, 2 clinicopathological situations, more or less intricated, may considerably complicate the management of these tumors and the patient health condition. Firstly, when the tumor is characterized by an usual aggressive behaviour with a possible extension within the cavernous sinus and a high risk of recurence after well- conducted treatment. Otherwise, in some cases of resistant prolactinomas and somatotropinomas, the specific medical treatment may be unsucessful for controlling the hormonal hypersecretion and/or the tumoral growth, with subsequent complex therapeutic approach.Progress that have been made in the understanding of aggressive as well as in resistant- to- treatment pituitary tumors, both in histopathology and molecular fields, may constitue new tools for improving knowledge on the profile of these atypical tumors and optimizing their management. © 2013 Elsevier Masson SAS. Source
Imbard A.,pitaux universitaires Paris Sud |
Boutron A.,pitaux universitaires Paris Sud |
Vequaud C.,pitaux universitaires Paris Sud |
Zater M.,pitaux universitaires Paris Sud |
And 5 more authors.
Molecular Genetics and Metabolism
Background: Pyruvate dehydrogenase complex (PDHc) deficiencies are an important cause of primary lactic acidosis. Most cases result from mutations in the X-linked gene for the pyruvate dehydrogenase E1α subunit (PDHA1) while a few cases result from mutations in genes for E1β (PDHB), E2 (DLAT), E3 (DLD) and E3BP (PDHX) subunits or PDH-phosphatase (PDP1). Aim: To report molecular characterization of 82 PDHc-deficient patients and analyze structural effects of novel missense mutations in PDHA1. Methods: PDHA1 variations were investigated first, by exon sequencing using a long range PCR product, gene dosage assay and cDNA analysis. Mutation scanning in PDHX, PDHB, DLAT and DLD cDNAs was further performed in unsolved cases. Novel missense mutations in PDHA1 were located on the tridimensional model of human E1 protein to predict their possible functional consequences. Results: PDHA1 mutations were found in 30 girls and 35 boys. Three large rearrangements, including two contiguous gene deletion syndrome were identified. Novel missense, frameshift and splicing mutations were also delineated and a nonsense mutation in a mosaic male. Mutations p.Glu75Ala, p.Arg88Ser, p.Arg119Trp, p.Gly144Asp, p.Pro217Arg, p.Arg235Gly, p.Tyr243Cys, p.Tyr243Ser, p.Arg245Gly, p.Pro250Leu, p.Gly278Arg, p.Met282Val, p.Gly298Glu in PDHA1 were predicted to impair active site channel conformation or subunit interactions. Six out of the seven patients with PDHB mutations displayed the recurrent p.Met101Val mutation; 9 patients harbored PDHX mutations and one patient DLD mutations. Conclusion: We provide an efficient stepwise strategy for mutation screening in PDHc genes and expand the growing list of PDHA1 mutations analyzed at the structural level. © 2011 Elsevier Inc. Source