A5069613706- Immunodeficiency and Autoimmune Disorders
- Inflammatory Bowel Disease
- Celiac Disease Research and Management
- Skin and Cellular Biology Research
- Digestive system and related health
- Autoimmune Bullous Skin Diseases
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Microscopic Colitis
- Genetic factors in colorectal cancer
- Eosinophilic Esophagitis
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Genomics and Rare Diseases
- Galectins and Cancer Biology
- Wnt/β-catenin signaling in development and cancer
- Hypertrophic osteoarthropathy and related conditions
- Genetic and rare skin diseases.
- Pancreatic function and diabetes
- Intestinal Malrotation and Obstruction Disorders
- T-cell and B-cell Immunology
- Peptidase Inhibition and Analysis
- Helicobacter pylori-related gastroenterology studies
- Congenital gastrointestinal and neural anomalies
- Chronic Lymphocytic Leukemia Research
Institut des Maladies Génétiques Imagine
2015-2025
Inserm
2016-2025
Université Paris Cité
2016-2025
Hôpital Necker-Enfants Malades
2016-2025
Assistance Publique – Hôpitaux de Paris
2016-2025
Institut Necker Enfants Malades
2022-2024
Sorbonne Paris Cité
2015-2022
Centre de Génétique Moléculaire
2021
Délégation Paris 5
2015-2020
Immunité et Cancer
2016-2017
Suppressor of cytokine signalling 1 (SOCS1) insufficiency is an inborn error immunity affecting the negative regulation and growth factor signalling. We aimed to enhance understanding clinical manifestations, disease trajectories, penetrance, effect Janus kinase (JAK) inhibition in individuals with SOCS1 insufficiency. This study used data from two independent cohorts: European Society for Immunodeficiencies (ESID) registry UK Biobank. Participants ESID were nine countries (Austria, Belgium,...
Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding p40phox subunit phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families 8 countries. These display different in-frame or out-of-frame that are homozygous 11 and compound heterozygous another. When overexpressed NB4 neutrophil-like cells EBV-transformed B vitro, mutant alleles were found to be LOF, with exception p.R58C c.120_134del alleles,...
An expanding number of monogenic defects have been identified as causative severe forms very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification known molecular diagnosis and adapt treatment.A total 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation VEO-IBD [n = 185]...
Propionic acidemia (PA) is a severe metabolic disorder with cardiac and neurologic complications poor quality of life. Liver transplantation (LT) was thus proposed in PA to increase enzyme activity. We studied retrospectively LT two European centers. Twelve patients underwent 17 LTs between 1991 2013. They developed severe, unusual unexpected complications, high mortality (58%). When present, the cardiomyopathy resolved no acute decompensation occurred allowing dietary relaxation. Renal...
ABSTRACT Objective: Early‐onset inflammatory bowel diseases can result from a wide spectrum of rare mendelian disorders. Early molecular diagnosis is crucial in defining treatment and improving life expectancy. Herein we aimed at the mechanism an immunodeficiency‐polyendrocrinopathy enteropathy‐X‐linked (IPEX)–like disease combined with severe immunodeficiency 2 siblings born distantly related parents. Methods: Whole exome sequencing was performed on blood‐extracted genomic DNA affected...
Research Article22 March 2018Open Access Source DataTransparent process Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis Marianna Parlato INSERM, UMR1163, Laboratory Intestinal Immunity Institut Imagine, Paris, France GENIUS group from ESPGHAN Search for more papers by this author Fabienne Charbit-Henrion Université Paris Descartes-Sorbonne Cité, Department Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Hôpital...
Objective: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disease caused by mutations in the forkhead box protein 3 gene (FOXP3), which encodes a key regulator of immune tolerance. The aim this study was to describe clinical heterogeneity national French cohort. Methods: Multicenter retrospective patients diagnosed with IPEX FOXP3. Results: Thirty children from 26 families were included. Age at onset (median [first third quartile]) 1.5 mo...
Abstract Background Very early-onset inflammatory bowel disease (VEOIBD), defined by IBD diagnosed before the age of 6 years, is a challenging condition with complex clinical features and limited long-term data. Our study describes outcome patients VEOIBD without any identified genetic mutation. Methods Data on all consecutive aged 0–6 years colitis (CD, UC, or IBD-U) at Necker-Enfants Malades Hospital (Paris, France) between 2013 2023 were retrospectively reviewed. Patients monogenic forms...
Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet mechanism underlying intestinal failure deficiency remains unclear. Here, biallelic variants were identified by next-generation sequencing 6 patients congenital diarrhea. Corroborating silico prediction, either abolished expression or altered protein conformation. Myosin VB was mass spectrometry as client of chaperone found misfolded UNC45AKO...
Anastomotic ulceration (AU) is a rare complication after intestinal resection and anastomosis, described mostly in children. The main symptom occult bleeding, leading to iron-deficiency anemia, which life threatening.The present survey reports series of patients with AU infancy, focusing on predictive factors, medical surgical treatment options, long-term outcomes. Eleven (7 boys) born between 1983 2005 an anastomosis infancy were included this retrospective review.The diagnosis was often...
Severe enterocolitis raises diagnostic and therapeutic challenges. Empirical treatment by steroids immunosuppressive drugs is commonly used but, to date, little attempt has been made specifically target the mechanism underlying inflammation. Possible causes of severe include refractory celiac disease,1Malamut G. et al.Gastroenterology. 2009; 136: 81-90Abstract Full Text PDF PubMed Scopus (305) Google Scholar autoimmune enteropathy,2Akram S. al.Clin Gastroenterol Hepatol. 2007; 5:...
Single genetic mutations predispose to very early onset inflammatory bowel disease (VEO-IBD). Here, we identify a de novo duplication of the 10p15.1 chromosomal region, including IL2RA locus, in 2-year-old girl with treatment-resistant pancolitis that was brought into remission by colectomy. Strikingly, after colectomy while patient clinical and without medication, peripheral blood CD4:CD8 ratio constitutively high CD25 expression increased on circulating effector memory, Foxp3+, Foxp3neg...
Hyper activation of the JAK-STAT signaling underlies pathophysiology many human immune-mediated diseases. Herein, study 2 adult patients with SOCS1 haploinsufficiency illustrates severe and pleomorphic consequences its impaired regulation in intestinal tract.Two unrelated presented gastrointestinal manifestations, one Crohn's disease-like ileo-colic inflammation refractory to anti-TNF other lymphocytic leiomyositis causing chronic pseudo-occlusion. Next-generation sequencing was used...
Abstract Variants in aminoacyl‐tRNA synthetases (ARSs) genes are associated to a broad spectrum of human inherited diseases. Patients with defective PheRS, encoded by FARSA and FARSB , display brain abnormalities, interstitial lung disease facial dysmorphism. We investigated four children from two unrelated consanguineous families carrying missense homozygous variants significantly reduced PheRS‐mediated aminoacylation activity. In addition the core ARS‐phenotype, all patients showed an...
Monogenic primary immunodeficiency syndromes can affect one or more endocrine organs by autoimmunity during childhood. Clinical manifestations include type 1 diabetes mellitus, hypothyroidism, adrenal insufficiency, and vitiligo. Lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency was described in 2012 as a novel immunodeficiency, predominantly causing immune dysregulation early onset enteropathy. We describe the heterogeneous clinical course of LRBA two siblings,...
Dysregulated transforming growth factor TGF-β signaling underlies the pathogenesis of genetic disorders affecting connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree dysmorphic features developmental delay well immune dysregulation; were from nine unrelated families. Importin 8 belongs to...
Background Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with risk of lethality, particularly infants. The clinical management NS challenging. Objectives To analyse the cohort infants managed reference centre to draw up recommendations for management. Methods We conducted monocentric analysis patients NS. inclusion criteria were our centre, histologically or molecularly confirmed...