Service de biochimie genetique
Service de biochimie genetique
Maazoun F.,Unite des maladies genetiques du globule rouge |
Gellen Dautremer J.,Unite des maladies genetiques du globule rouge |
Boutekadjirt A.,Service dimagerie medicale |
Pissard S.,Service de biochimie genetique |
And 8 more authors.
Revue de Medecine Interne | Year: 2016
Introduction: Symptomatic extramedullary hematopoiesis (EH) is a rare but potentially severe phenomenon which occurs in β-thalassemia. There are no treatment guidelines. Methods: Retrospective single centre study including the cases of symptomatic EH encountered between 1997 and 2014 in a unit specialised in red blood cell genetic disorders. Description of clinical, biological and radiological characteristics of the patients, treatments received, and outcomes. Results: Among 182 β-thalassemia patients followed during the study period, 7 cases of symptomatic EH were diagnosed. They were 5 men and 2 women, and their mean age was 37 years. Four patients were splenectomised, two patients were regularly transfused, and four patients had already received erythropoietin. EH was localised in intravertebral areas and responsible for dorsal spinal cord compression in 5 patients, in paravertebral dorsal area in 1 patient, and in presacral area in 1 patient. The mean hemoglobin level at diagnosis was 7.9 g/dL. Treatment administered included: red cell transfusion in 6 cases, associated with hydroxyurea in 5 cases and/or radiotherapy in 3 patients. One patient was treated with surgery and HU. After a median follow-up of 41 months, clinical recovery was complete in 2 patients and partial in 5 patients. Conclusion: EH must be suspected in β-thalassemia in patients presenting clinical signs of organ compression, and a typical radiological aspect. The functional prognosis depends on the rapidity of treatment, which includes red blood cell transfusion, hydroxyurea, radiotherapy, and rarely surgery. Long-term outcome is uncertain. © 2015.
Sermet-Gaudelus I.,French Institute of Health and Medical Research |
Brouard J.,Caen University Hospital Center |
Brouard J.,University of Caen Lower Normandy |
Renouil M.,Groupe hospitalier Sud Reunion |
And 12 more authors.
Archives de Pediatrie | Year: 2014
These guidelines aim to standardize the care of infants diagnosed with a typical form of cystic fibrosis (CF) at neonatal screening. They have been implemented by the National Working Group for Neonatal Screening of the French Federation for CF and have been validated using the Delphi methodology by a large group of clinicians involved in the care of CF infants. These guidelines encompass management and organization of care at diagnosis and describe nutritional, digestive, and respiratory monitoring and treatment during the first 2 years of life. © 2014 Elsevier Masson SAS.
Sermet-Gaudelus I.,University of Paris Descartes |
Girodon E.,Groupe Hospitalier Henri Mondor Albert Chenevier |
Sands D.,Institute of Mother and Child |
Vavrova V.,Charles University |
And 5 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010
Rationale: The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with a sweat chloride (Cl -) concentration greater than 60 mmol/L or the identification of two CF-causing mutations. A challenging problem is the significant number of children for whom no definitive diagnosis is possible because they present with symptoms suggestive of CF, a sweat chloride level in the intermediate range between 30 and 60 mmol/L, and only one or no identified CF-causing mutation. Objectives: To investigate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways of children with intermediate sweat tests and inconclusive genetic findings in correlation with clinical phenotype and genotype. Methods: We developed a composite nasal potential difference (NPD) diagnostic score to discriminate patients with CF from non-CF patients. We tested NPD in 50 children (age, 6 mo to 18 yr) with equivocal diagnoses and correlated the NPD diagnostic score with clinical phenotypes and genotypes. Measurements and Main Results: Fifteen of the 50 children had NPD scores in the CF range. Eight of the 15 carried two CFTR mutations compared with only 5 of the 35 children with normal NPD scores (P= 0.01). They were significantly younger at evaluation and had recurrent lower respiratory tract infections, chronic productive coughs, and chronic Staphylococcus aureus colonization significantly more often than the 35 children with normal NPD results. Conclusions: Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.
PubMed | Service dimagerie medicale, Service de biochimie genetique, Unite des maladies genetiques du globule rouge, Service de medecine interne and Service de radiotherapie
Type: Case Reports | Journal: La Revue de medecine interne | Year: 2015
Symptomatic extramedullary hematopoiesis (EH) is a rare but potentially severe phenomenon which occurs in -thalassemia. There are no treatment guidelines.Retrospective single centre study including the cases of symptomatic EH encountered between 1997 and 2014 in a unit specialised in red blood cell genetic disorders. Description of clinical, biological and radiological characteristics of the patients, treatments received, and outcomes.Among 182 -thalassemia patients followed during the study period, 7cases of symptomatic EH were diagnosed. They were 5men and 2women, and their mean age was 37years. Four patients were splenectomised, two patients were regularly transfused, and four patients had already received erythropoietin. EH was localised in intravertebral areas and responsible for dorsal spinal cord compression in 5patients, in paravertebral dorsal area in 1patient, and in presacral area in 1patient. The mean hemoglobin level at diagnosis was 7.9g/dL. Treatment administered included: red cell transfusion in 6 cases, associated with hydroxyurea in 5 cases and/or radiotherapy in 3patients. One patient was treated with surgery and HU. After a median follow-up of 41months, clinical recovery was complete in 2patients and partial in 5patients.EH must be suspected in -thalassemia in patients presenting clinical signs of organ compression, and a typical radiological aspect. The functional prognosis depends on the rapidity of treatment, which includes red blood cell transfusion, hydroxyurea, radiotherapy, and rarely surgery. Long-term outcome is uncertain.
da Paz J.A.,University of Sao Paulo |
Kim C.A.,University of Sao Paulo |
Goossens M.,Service de Biochimie Genetique |
Giurgea I.,Service de Biochimie Genetique |
Marques-Dias M.J.,University of Sao Paulo
Arquivos de Neuro-Psiquiatria | Year: 2015
Objective: To present a seven-cases serie of Mowat-Wilson syndrome (MWS).Method: All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization.Results: A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6). The EEG showed epileptic focal activity (5/7). The imaging studies revealed total agenesis (4/7) and partial agenesis of the corpus callosum (1/7).Conclusion: Physicians who care for patients with mental retardation and epilepsy should be aware of SMW. © 2015, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.
Raymond L.,Hopitaux Universitaires Paris sud |
Francou B.,Genetique moleculaire |
Petit F.,Hopitaux Universitaires Paris Sud |
Tosca L.,Hopitaux Universitaires Paris sud |
And 15 more authors.
European Journal of Medical Genetics | Year: 2015
We report the prenatal detection of a de novo unbalanced complex chromosomal rearrangement (CCR), in a fetus with growth delay and bilateral cataracts. Standard karyotype and FISH analyses on amniotic fluid revealed a complex de novo translocation, resulting in a 46,XY,t(1;12;14)(q42;q14;q32) karyotype. CGH-array showed a significant deletion of 387 kb at 12q14.3, at a distance of only 200e700 kb from the breakpoint at 12q14, which encompassed the HMGA2 gene and occurred de novo. Although 12q14 microdeletions are associated with growth delay in several reports in the literature, we present here the smallest deletion prenatally detected, and we detail the clinical description of the fetus. The correlation between cataracts and this complex genotype is puzzling. Among the genes disrupted by the breakpoint in 12q14, GRIP1 has been associated with abnormal eye development in mice, including lens degeneration. Interestingly, HMGA2 is expressed in the mouse's developing lens, and its expression is decreased in lens of elderly humans, correlated with the severity of lens opacity. In this report, we refine the link between HMGA2 loss of function and growth delay during prenatal development. We also discuss the correlation between cataracts and genotype in this unbalanced CCR case of unexpected complexity. © 2015 Elsevier Masson SAS.
Wentzel C.,Uppsala University |
Rajcan-Separovic E.,University of British Columbia |
Ruivenkamp C.A.L.,Leiden University |
Chantot-Bastaraud S.,Service de Genetique |
And 14 more authors.
European Journal of Human Genetics | Year: 2011
With the clinical implementation of genomic microarrays, the detection of cryptic unbalanced rearrangements in patients with syndromic developmental delay has improved considerably. Here we report the molecular karyotyping and phenotypic description of six new unrelated patients with partially overlapping microdeletions at 10p12.31p11.21 ranging from 1.0 to 10.6 Mb. The smallest region of overlap is 306 kb, which includes WAC gene, known to be associated with microtubule function and to have a role in cell division. Another patient has previously been described with a 10 Mb deletion, partially overlapping with our six patients. All seven patients have developmental delay and a majority of the patients have abnormal behaviour and dysmorphic features, including bulbous nasal tip, deep set eyes, synophrys/thick eyebrows and full cheeks, whereas other features varied. All patients also displayed various visual impairments and six out of seven patients had cardiac malformations. Taken together with the previously reported patient, our study suggests that the detected deletions may represent a new contiguous gene syndrome caused by dosage-sensitive genes that predispose to developmental delay. © 2011 Macmillan Publishers Limited All rights reserved.