Search results for "1311"
showing 10 items of 39 documents
Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene
2002
In the field of occupational and/or environmental toxicology, the measurement of specific metabolites in urine may serve to assess exposure to the parent compounds (biological monitoring of exposure). Styrene is one of the chemicals for which biological monitoring programs have been validated and implemented in environmental and occupational medicine. However, inter-individual differences in the urinary excretion exist both for the main end-products (mandelic acid and phenylglyoxylic acid) and for its specific mercapturic acids (phenylhydroxyethylmercapturic acids, PHEMA). This limits to a certain extent the use of these metabolites for an accurate assessment of styrene exposure. In a group…
Variable pulmonary manifestations in Chitayat syndrome: Six additional affected individuals
2020
Hand hyperphalangism leading to shortened index fingers with ulnar deviation, hallux valgus, mild facial dysmorphism and respiratory compromise requiring assisted ventilation are the key features of Chitayat syndrome. This condition results from the recurrent heterozygous missense variant NM_006494.2:c.266A>G; p.(Tyr89Cys) in ERF on chromosome 19q13.2, encoding the ETS2 repressor factor (ERF) protein. The pathomechanism of Chitayat syndrome is unknown. To date, seven individuals with Chitayat syndrome and the recurrent pathogenic ERF variant have been reported in the literature. Here, we describe six additional individuals, among them only one presenting with a history of assisted ventil…
Recommendations on the diagnosis and management of Niemann-Pick disease type C
2009
Niemann-Pick disease type C (NP-C) is a lysosomal storage disease in which impaired intracellular lipid trafficking leads to excess storage of cholesterol and glycosphingolipids in the brain and other tissues. it is characterized clinically by a variety of progressive, disabling neurological symptoms including clumsiness, limb and gait ataxia, dysarthria, dysphagia and cognitive deterioration (dementia). Until recently, there has been no disease-modifying therapy available for NP-C, with treatment limited to supportive measures. In most countries, NP-C is managed through specialist centers, with non-specialist support provided locally. However, effective patient Support is hampered by the a…
Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort
2013
The work conducted at the WTCHG was supported by Wellcome Trust grants [076566/Z/05/Z] and [075491/Z/04]; the work in Zurich partly by an SNSF grant [32-108130]. We also thank MAF (Mutation Analysis core Facility) at the Karolinska Institute, Novum, Huddinge. The French part of the project was funded by Agence Nationale de la Recherche (ANR-06-NEURO-019-01 GENEDYS) and Ville de Paris. S Paracchini is a Royal Society University Research Fellow. D Czamara was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy). Dyslexia is one of the most common childhood disorders with a prevalence o…
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
2010
We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with gen…
The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle
2015
12 páginas, 4 figuras, 2 tablas.
What is the impact of rerouting a cancer diagnosis from emergency presentation to GP referral on resource use and survival? Evidence from a populatio…
2018
Background Studies on alternative routes to diagnosis stimulated successful policy interventions reducing the number of emergency diagnoses and associated mortality risk. A dearth of evidence on the costs of such interventions might prevent new policies from achieving more ambitious targets. Methods We conducted a retrospective cohort study on the population of colorectal (88,051), breast (90,387), prostate (96,219), and lung (97,696) cancer patients diagnosed after a GP referral or an emergency presentation and reported in the Cancer Registry of England. Resource use and survival were compared 1 year before and 5 years after diagnosis (3 years for lung), including the costs of GP referrals…
Detection of primary DNA damage: applicability to biomonitoring of genotoxic occupational exposure and in clinical therapy
1995
The biological effect of putative genotoxic chemicals in the work place environment was monitored in peripheral mononuclear blood cells of exposed workers. DNA strand breaks, alkali-labile sites of DNA and DNA cross-links were measured using the alkaline filter elution method. A dose dependent increase in DNA damage was found in sterilization workers exposed to ethylene oxide and metal workers with exposure towards N-nitrosodiethanolamine. Two subpopulations with different response to the external exposure were found in nonsmoking sterilization workers. Nurses handling antineo-plastic agents without adequate safety provisions showed a statistically significantly higher rate of DNA strand br…
Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis.
2012
Familial idiopathic basal ganglia calcification (IBGC) is a genetic condition with a wide spectrum of neuropsychiatric symptoms, including parkinsonism and dementia. Here, we identified mutations in SLC20A2, encoding the type III sodium-dependent phosphate transporter 2 (PiT2), in IBGC-affected families of varied ancestry, and we observed significantly impaired phosphate transport activity for all assayed PiT2 mutants in Xenopus laevis oocytes. Our results implicate altered phosphate homeostasis in the etiology of IBGC.
Meta-analysis and imputation refines the association of 15q25 with smoking quantity.
2010
Smoking is a leading global cause of disease and mortality(1). We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a …