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Sevilla, Spain

Zafra-Gomez A.,University of Granada | Luzon-Toro B.,Unit of Genetics | Jimenez-Diaz I.,University of Granada | Ballesteros O.,University of Granada | Navalon A.,University of Granada
Journal of Pharmaceutical and Biomedical Analysis | Year: 2010

A gas chromatographic-mass spectrometric (GC-MS) method for qualitative and subsequent quantitative analysis of phenolic antioxidants compounds, presents in olive oil, in rat cerebrospinal fluid (CSF) after oral administration of compounds is proposed. The procedure involves the extraction of compounds from the samples by a traditional microliquid-liquid extraction method, followed by a silylation step before the GC-MS analysis. The chromatographic separation was performed by using a low bleed DB5-MS fused-silica capillary column. The presence of 21 phenolic compounds was tested in CSF extracts and only free tyrosol, hydroxytyrosol and ferulic acid were detected. Those compounds were then quantitatively determined using the proposed methology. The molecular ion for silylated compounds appears at 370m/z for hydroxytyrosol, 282m/z for tyrosol and 338m/z for ferulic acid respectively, while the base peak appears at 267m/z, 179m/z and 338 m/z α-Naphthol was used as a surrogate (216 and 201m/z). The detection capabilities obtained were 74, 92 and 79ng/mL respectively. The method was applied to the determination of trace amounts of compounds in rat cerebrospinal fluid after oral administration. The animals were fed with a standard chow diet (free of phenolic antioxidants) in order to avoid the influence of any other component of the diet on the CSF of the animals. © 2010 Elsevier B.V. Source


Lavoine N.,Gustave Roussy Cancer Campus | Colas C.,Pitie Salpetriere University Hospital | Colas C.,French Institute of Health and Medical Research | Colas C.,Paris-Sorbonne University | And 35 more authors.
Journal of Medical Genetics | Year: 2015

Background Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. Methods Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. Results 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26-213.2). Failure rate seemed to be higher than expected especially for Tcell non-Hodgkin's lymphoma ( progression/relapse in 6/ 12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). Conclusions In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance. Source


Van Den Ouweland A.M.W.,Erasmus Medical Center | Elfferich P.,Erasmus Medical Center | Zonnenberg B.A.,UMC Utrecht | Arts W.F.,Erasmus Medical Center | And 6 more authors.
European Journal of Human Genetics | Year: 2011

Tuberous sclerosis complex (TSC), an autosomal dominant disorder, is a multisystem disease with manifestations in the central nervous system, kidneys, skin and/or heart. Most TSC patients carry a pathogenic mutation in either TSC1 or TSC2. All types of mutations, including large rearrangements, nonsense, missense and frameshift mutations, have been identified in both genes, although large rearrangements in TSC1 are scarce. In this study, we describe the identification and characterisation of eight large rearrangements in TSC1 using multiplex ligation-dependent probe amplification (MLPA) in a cohort of 327 patients, in whom no pathogenic mutation was identified after sequence analysis of both TSC1 and TSC2 and MLPA analysis of TSC2. In four families, deletions only affecting the non-coding exon 1 were identified. In one case, loss of TSC1 mRNA expression from the affected allele indicated that exon 1 deletions are inactivating mutations. Although the number of TSC patients with large rearrangements of TSC1 is small, these patients tend to have a somewhat milder phenotype compared with the group of patients with small TSC1 mutations. © 2011 Macmillan Publishers Limited All rights reserved. Source


Bladen C.L.,Institute of Genetic Medicine | Rafferty K.,Institute of Genetic Medicine | Straub V.,Institute of Genetic Medicine | Monges S.,Hospital Pediatria J. P. Garrahan | And 59 more authors.
Human Mutation | Year: 2013

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry. © 2013 WILEY PERIODICALS, INC. Source

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