Moortgat S.,Institute Of Pathologie Et Of Genetique |
Verellen-Dumoulin C.,Institute Of Pathologie Et Of Genetique |
Maystadt I.,Institute Of Pathologie Et Of Genetique |
Parmentier B.,Institute Of Pathologie Et Of Genetique |
And 3 more authors.
European Journal of Medical Genetics | Year: 2011
Interstitial deletions of the long arm of chromosome 3 are rare and detailed genotype-phenotype correlations are not well established. We report on the clinical, cytogenetic and molecular findings of a 5-year-old patient with a de novo interstitial deletion from 3q25.1 to 3q25.32. Clinical features include relative microcephaly, developmental delay and facial dysmorphism with a coarse face, ptosis, synophrys, epicanthic folds, broad nasal bridge, long philtrum, large mouth with full lips, dysplastic and low-set ears.Revealed by conventional banding techniques, the deleted region of 8.9 Mb was confirmed by fluorescent in situ hybridization (FISH) analyses and array comparative genomic hybridization (array-CGH). To our knowledge, this is the smallest interstitial deletion reported in the 3q25 region. The phenotype of our patient is compared with the 10 previously reported cases implicating the 3q25 region. © 2010.
Kraus M.R.-C.,Ecole Polytechnique Federale de Lausanne |
Clauin S.,University Pierre and Marie Curie |
Pfister Y.,Ecole Polytechnique Federale de Lausanne |
Di Maio M.,Departement de pediatrie |
And 4 more authors.
Human Mutation | Year: 2012
Bicaudal C homologue 1 (Bicc1) knockout in mice causes polycystic kidney disease and pancreas development defects, including a reduction in insulin-producing β-cells and ensuing diabetes. We therefore screened 137 patients with renal abnormalities or association of earlyonset diabetes and renal disease for genetic alterations in BICC1. We identified two heterozygous mutations, one nonsense in the first K Homology (KH) domain and one missense in the sterile alpha motif (SAM) domain. Inmice, Bicc1 blocks canonical Wnt signaling, mostly via its SAM domain. We show that the human BICC1, similar to its mouse counterpart, blocks canonical Wnt signaling. The nonsense mutation identified results in a complete loss of Wnt inhibitory activity. The point mutation in the SAM domain has a similar effect to a complete SAM domain deletion, resulting in a 22% loss of activity. © 2011 Wiley Periodicals, Inc.
Chargui J.,Innate Pharma |
Combaret V.,French Institute of Health and Medical Research |
Scaglione V.,Innate Pharma |
Iacono I.,French Institute of Health and Medical Research |
And 9 more authors.
Journal of Immunotherapy | Year: 2010
Gamma/delta T cells (Vγ9δ2) contribute to innate immunity and exert natural cytotoxicity against a variety of tumors. Using a synthetic phosphoantigen (Bromohydrin Pyrophosphate, BrHPP), we amplified Vγ9δ2 T cells in vitro from neuroblastoma patients. In the presence of BrHPP and low doses of IL-2, robust proliferation of Vγ9δ2 T cells was obtained from peripheral blood mononuclear cells (PBMC) harvested at diagnosis. Moderate proliferation was observed from PBMC harvested after stem cell transplantation, whereas modest levels of Vγ9δ2 T cells were obtained from PBMC harvested after induction therapy. Proliferation was observed after a single in vitro stimulation with BrHPP. After 21 days in culture, Vγ9δ2 T cells represented more than 80% of cultured cells (a 50-fold expansion from baseline). Moreover, BrHPP-amplified Vγ9δ2 T cells from patients-expressed activation markers and were able to lyse allogeneic and autologous neuroblasts. This cytotoxic activity was γδ T-cell receptor-dependent. Clinical trials using BrHPP are warranted in patients with poor-prognosis neuroblastoma, either to expand patient-derived Vγ9δ2 T cells ex vivo or by direct administration to in vivo to boost the pool of resident Vγ9δ2 T cells in vivo. Copyright © 2010 by Lippincott Williams & Wilkins.
Rudant J.,University Paris - Sud |
Orsi L.,University Paris - Sud |
Monnereau A.,University Paris - Sud |
Monnereau A.,Institute Bergonie |
And 17 more authors.
International Journal of Cancer | Year: 2011
The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case-control study, Escale, was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR = 0.5 (0.2-1.2)] and between HL and repeated early common infections among non-breastfed children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5-2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5 (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history of asthma [OR = 0.6 (0.3-1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations. © 2010 UICC.
Grimaldi C.,Marseille University Hospital Center |
Bremont F.,Departement de pediatrie |
Berlioz-Baudoin M.,Nice University Hospital Center |
Brouard J.,Caen University Hospital Center |
And 10 more authors.
European Journal of Pediatrics | Year: 2015
The influence of the generalization of cystic fibrosis newborn screening (CFNBS) in France on sweat test (ST) prescription is unknown. In this French retrospective, descriptive, and multicenter study, we studied the indications, number, methods, and results of STs prescribed by a pediatric pulmonologist in children who had a negative CFNBS and an ST for respiratory symptoms in 2012. We included 502 children with 523 STs, performed with four different methods. The main indication was asthma (71.3 %), then chronic cough (52.4 %), atypical lower airway infections (42.2 %), and bronchiectasis (7 %). Four children had a diagnosis of CF (0.8 %), all presenting with chronic productive cough and recurrent respiratory infections. Conclusion: Asthma is the most frequent indication of ST in our cohort. Because of the systematic CFNBS in France, some prescriptions should be avoided, particularly in case of severe or moderate asthma with no other associated symptom. Moreover, methods of STs often do not follow the guidelines and need standardization.What is Known:• Newborn screening (NBS) has become the most frequent circumstance of the diagnosis of cystic fibrosis (CF) in France after its generalization.• The prescription of sweat test (ST) in children with respiratory symptoms who already had a negative NBS has not been studied.What is New:• In children with a negative CF NBS referred to a university hospital for respiratory diseases, despite important variations of ST methods, only 4 children among 502 have been diagnosed as CF.• Despite recommendations, ST prescription should be avoided in children with moderate to severe asthma and no other associated symptom. © 2015, Springer-Verlag Berlin Heidelberg.