Gras D.,AP HP |
Jonard L.,Laboratoire Of Biochimie Biologie Moleculaire |
Roze E.,AP HP |
Roze E.,French National Center for Scientific Research |
And 31 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2012
Background: Benign hereditary chorea (BHC) is a rare autosomal dominant disorder characterised by childhood onset that tends to improve in adulthood. The associated gene, NKX2-1 (previously called TITF1), is essential for organogenesis of the basal ganglia, thyroid and lungs. The aim of the study was to refine the movement disorders phenotype. We also studied disease course and response to therapy in a large series of genetically proven patients. Methods: We analysed clinical, genetic findings and follow-up data in 28 NKX2-1 mutated BHC patients from 13 families. Results: All patients had private mutations, including seven new mutations, three previously reported mutations and three sporadic deletions encompassing the NKX2-1 gene. Hypotonia and chorea were present in early infancy, with delayed walking ability (25/28); dystonia, myoclonus and tics were often associated. Attention deficit hyperactivity disorder (ADHD) was present in seven. Among the 14 patients followed-up until adulthood, nine had persistent mild chorea, two had near total resolution of chorea but persistent disabling prominent myoclonus and three recovered completely. Learning difficulties were observed in 20/28 patients, and three had mental retardation. Various combinations of BHC, thyroid (67%) and lung (46%) features were noted. We found no genotype-phenotype correlation. A rapid and sustained beneficial effect on chorea was obtained in 5/8 patients treated with tetrabenazine. Conclusion: Early onset chorea preceded by hypotonia is suggestive of BHC. Associated thyroid or respiratory disorders further support the diagnosis and call for genetic studies. Tetrabenazine may be an interesting option to treat disabling chorea.
Boyer J.-C.,Nimes University Hospital Center |
Etienne-Grimaldi M.-C.,Center Antoine Lacassagne |
Thomas F.,Institute Claudius Regaud |
Quaranta S.,Marseille University Hospital Center |
And 10 more authors.
Bulletin du Cancer | Year: 2014
Irinotecan is a cytotoxic agent administered by IV infusion in the treatment of advanced colorectal cancer. Its anticancer activity results from its bioactivation into SN-38 metabolite, which is cleared through glucuronidation by the hepatic enzyme uridine diphosphate- glucuronosyltransferase 1A1 (UGT1A1). In the general population, there is wide inter-subject variability in UGT1A1 enzyme activity related to UGT1A1 gene polymorphisms. The French joint workgroup coming from the National Pharmacogenetic Network (RNPGx) and the Group of Clinical Oncologic Pharmacology (GPCO) herein presents an updated review dealing with efficacy and toxicity clinical studies related to UGT1A1 genetic variants. From a critical analysis of this review it clearly emerges that, for doses higher than 180 mg/m 2, hematologic and digestive irinotecan-induced toxicities could be prevented in daily clinical practice by generalizing the use of a simple pharmacogenetic test before starting treatment. The clinical relevance of this test is also discussed in terms of treatment efficacy improvement, with the possibility of increasing the irinotecan dose in patients not bearing the deleterious allele. This test involves using a blood sample to analyze the promoter region of the UGT1A1 gene (UGT1A1*28 allele). Best execution practices, laboratory costs, as well as results interpretation are described with the aim of facilitating the implementation of this analysis in clinical routine. The existence of a French laboratories network performing this test in clinical routine makes it possible to generalize UGT1A1 deficiency screening, so as to guarantee equal access to safe treatment and optimized irinorecan-based therapy for the many patients receiving irinotecan-based therapy in advanced colorectal cancer. ©John Libbey Eurotext.
Riahi Z.,Institute Pasteur Of Tunis |
Riahi Z.,Tunis el Manar University |
Hammami H.,Service dOrl et de Chirurgie Maxillo faciale |
Ouragini H.,Institute Pasteur Of Tunis |
And 12 more authors.
Gene | Year: 2013
Hearing loss is the most frequent sensory disorder. It affects 3 in 1000 newborns. It is genetically heterogeneous with 60 causally-related genes identified to date. Mutations in GJB2 gene account for half of all cases of non-syndromic deafness. The aim of this study was to determine the relative frequency of GJB2 allele variants in Tunisia. In this study, we screened 138 patients with congenital hearing loss belonging to 131 families originating from different parts of Tunisia for mutations in GJB2 gene. GJB2 mutations were found in 39% of families (51/131). The most common mutation was c.35delG accounting for 35% of all cases (46/131). The second most frequent mutation was p.E47X present in 3.8% of families. Four identified mutations in our cohort have not been reported in Tunisia; p.V37I, c.235delC, p.G130A and the splice site mutation IVS1+1G>A (0.76%). These previously described mutations were detected only in families originating from Northern and not from other geographical regions in Tunisia. In conclusion we have confirmed the high frequency of c.35delG in Tunisia which represents 85.4% of all GJB2 mutant alleles. We have also extended the mutational spectrum of GJB2 gene in Tunisia and revealed a more pronounced allelic heterogeneity in the North compared to the rest of the country. © 2013 Elsevier B.V.
Zerimech F.,Laboratoire Of Biochimie Biologie Moleculaire |
Huyvaert H.,Laboratoire Of Biochimie Biologie Moleculaire |
Matran R.,University of Lille Nord de France |
Matran R.,Laboratoire dExploration Fonctionnelle |
And 2 more authors.
Clinical Biochemistry | Year: 2011
Objectives: We checked the efficiency of a new dialysis device adapted to small volumes to remove glycerol from cryopreserved red blood cells. Design and methods: Dialysis was performed on D-Tube96™ Dialyzer Mini device. In a preliminary trial, we measured the residual glycerol before, and 2, 4 and 24 h after dialysis. Glycerol and hemoglobin concentrations and antioxidant enzymes activities were measured in three samples with or without glycerolization/deglycerolization procedure. The mini dialysis was then applied to 96 samples from the French Epidemiological study on the Genetics and Environment of Asthma. Results: Ninety-two percent of glycerol was removed after 24 h of dialysis. Hemoglobin content and activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were recovered. No significant loss of volume was observed. Results obtained for the 96 samples perfectly fitted with reference values of our laboratory. Conclusion: This new dialysis method seems to be particularly adapted for processing a large number of samples of RBCs cryoconserved in small volumes from epidemiological studies. © 2011 The Canadian Society of Clinical Chemists.
Belzeaux R.,Aix - Marseille University |
Belzeaux R.,Pole Of Psychiatrie University Solaris |
Bergon A.,Pole Of Psychiatrie University Solaris |
Bergon A.,French Institute of Health and Medical Research |
And 22 more authors.
Translational Psychiatry | Year: 2012
To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis. © 2012 Macmillan Publishers Limited All rights reserved.