A5035798496- Pancreatic function and diabetes
- Genetics and Neurodevelopmental Disorders
- Metabolism, Diabetes, and Cancer
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Cerebrovascular and genetic disorders
- Autism Spectrum Disorder Research
- Lipoproteins and Cardiovascular Health
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- RNA modifications and cancer
- Congenital heart defects research
- Diabetes Treatment and Management
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Genetic Mapping and Diversity in Plants and Animals
- Machine Learning in Bioinformatics
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Genetic factors in colorectal cancer
- Moyamoya disease diagnosis and treatment
- Cholesterol and Lipid Metabolism
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Nutrition, Genetics, and Disease
Inserm
1997-2024
Université Paris Cité
2014-2024
Institut Cochin
2021-2024
Centre National de la Recherche Scientifique
1995-2024
Délégation Paris 7
2014-2021
Sorbonne Paris Cité
2014-2017
Sorbonne Université
2017
NeuroDiderot
2015
Physiopathologie et Epidémiologie des Maladies Respiratoires
2015
Klinikum Stuttgart
2011
We screened 71 sporadic and 7 familial Rett syndrome (RTT) patients for MECP2 mutations by direct sequencing determined the pattern of X chromosome inactivation (XCI) in 39 RTT patients. identified 23 different disease-causing 54 (76%) 2 (29%) cases. compared electrophysiological findings, cerebrospinal fluid neurochemistry, 13 clinical characteristics between carrying missense those truncating mutations. Thirty-one 34 (91%) with classic had random XCI. Nonrandom XCI was associated milder...
G protein-coupled receptor (GPCR) activation mediated by ligand-induced structural reorganization of its helices is poorly understood. To determine the universal elements this conformational switch, we used evolutionary tracing (ET) to identify residue positions commonly important in diverse GPCRs. When mapped onto rhodopsin structure, these trace residues cluster into a network contacts from retinal binding site protein-coupling loops. Their roles generic transduction mechanism were...
Cerebral small vessel disease represents a heterogeneous group of disorders leading to stroke and cognitive impairment. While most diseases appear sporadic related age hypertension, several early-onset monogenic forms have also been reported. However, only minority patients with familial carry mutations in one known genes. We used whole exome sequencing identify candidate genes an autosomal dominant family which had excluded, subsequently screened all 201 unrelated probands unknown...
Obesity is one of the most significant risk factors for hypertension, coronary heart disease, and NIDDM (Frayn KN, Coppack SW: Insulin resistance, adipose tissue disease. Clin Sci 82:1–8, 1992; Kaplan NM: The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia, hypertension. Arch Intern Med 149:1514–1520, 1989). While family segregation, adoption, twin studies have indicated that degree adiposity has a genetic component (Stunkard AJ, Harris JR, Pedersen NL, McClearn...
Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure diabetes. Here, we report the first homozygous mutation in PPP1R15B gene (also known as constitutive repressor eIF2α [CReP]) encoding regulatory subunit an eIF2α-specific phosphatase two siblings affected by a novel syndrome diabetes youth short stature, intellectual disability, microcephaly. The R658C affects conserved amino acid...
Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by hyperglycemia resulting from defects in insulin secretion and action. Recent studies have found mutations the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) families with maturity-onset of young (MODY), an autosomal dominant form early age at onset defect glucose-stimulated secretion. During course our search for susceptibility genes contributing to more common late-onset NIDDM forms, we...
Autism spectrum disorders (ASDs) are common, heritable, but genetically heterogeneous neurodevelopmental conditions. We recently defined a susceptibility locus for ASDs on chromosome 1q41-q42. High-resolution single-nucleotide polymorphisms (126 SNPs) genotyping across the 1q41-q42 region, followed by MARK1 (microtubule affinity-regulating kinase 1)-tagged-SNP association study in 276 families with autism from Genetic Research Exchange, showed that several SNPs within gene were significantly...
Objective DNAJC3 , also known as P58 IPK is an Hsp40 family member that interacts with and inhibits PKR-like ER-localized eIF2α kinase (PERK). Dnajc3 deficiency in mice causes pancreatic β-cell loss diabetes. Loss-of-function mutations cause early-onset diabetes multisystemic neurodegeneration. The aim of our study was to investigate the genetic syndromic two unrelated patients, elucidate mechanisms failure this syndrome. Methods Whole exome sequencing performed identified variants were...
The sulfonylurea receptor (SUR) is a key component in glucose-stimulated insulin secretion. Obesity and NIDDM are frequently associated share some metabolic abnormalities, suggesting that they might also susceptibility genes. Thus, the SUR encoding gene plausible candidate for primary pancreatic β-cell defect thus hyperglycemia weight gain. Through association linkage studies, we have investigated potential role of families with two independent sets morbidly obese families. exon 22 T-allele...
How conserved pathways are differentially regulated to produce diverse outcomes is a fundamental question of developmental and evolutionary biology. The process neural precursor cell (NPC) selection by basic helix-loop-helix (bHLH) proneural transcription factors in the peripheral nervous system (PNS) atonal related proteins (ARPs) presents an excellent model which address this issue. Proneural ARPs belong two highly groups: ATONAL (ATO) group NEUROGENIN (NGN) group. We used cross-species...
We screened 71 sporadic and 7 familial Rett syndrome (RTT) patients for MECP2 mutations by direct sequencing determined the pattern of X chromosome inactivation (XCI) in 39 RTT patients. identified 23 different disease-causing 54 (76%) 2 (29%) cases. compared electrophysiological findings, cerebrospinal fluid neurochemistry, 13 clinical characteristics between carrying missense those truncating mutations. Thirty-one 34 (91%) with classic had random XCI. Nonrandom XCI was associated milder...
As part of an ongoing search for susceptibility loci NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action linkage with NIDDM. Loci included the G-protein–coupled inwardly rectifying potassium channels expressed β-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R), LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein convertase 2 (PCSK2), cholecystokinin B (CCKBR},...
Abstract Background Autism is a complex, heterogeneous, behaviorally-defined disorder characterized by disruptions of the nervous system and other systems such as pituitary-hypothalamic axis. In previous genome wide screen, we reported linkage autism with 1.2 Megabase interval on chromosome 5q31. For current study, hypothesized that 3 genes in this region could be involved development autism: 1) paired-like homeodomain transcription factor 1 ( PITX1 ), which key regulator hormones within...
Primary hypercholesterolemia is characterized by elevated LDL-cholesterol (LDL-C) levels isolated in autosomal dominant (ADH) or associated with triglyceride familial combined hyperlipidemia (FCHL). Rare APOE variants are known ADH and FCHL. We explored the molecular spectrum a French ADH/FCHL cohort of 5743 unrelated probands. The sequencing LDLR, PCSK9, APOB, revealed 76 carriers rare variant, no mutation APOB. Among 31 identified here, 15 described ADH, 10 FCHL, 6 both Five were...
We describe a new syndrome characterized by early-onset diabetes associated with bone marrow failure, affecting mostly the erythrocytic lineage. Using whole-exome sequencing in remotely consanguineous patient from family two affected siblings, we identified single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located dUTPase (DUT) gene (National Center for Biotechnology Information Gene ID 1854), both mitochondrial (DUT-M p.Y142C) and nuclear (DUT-N p.Y54C) isoforms. found...
Background: The LDLR (low-density lipoprotein receptor) in the liver is major determinant of LDL-cholesterol levels human plasma. discovery genes that regulate activity helps to identify pathomechanisms hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease. Methods: We performed a genome-wide RNA interference screen for limiting uptake fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit were validated by vitro experiments as well analyses...
Previous segregation analysis of a sample 234 randomly selected Australian families showed evidence for recessive major gene controlling serum immunoglobulin E (IgE) levels independently the specific response to allergens (SRA). Since linkage has been recently reported between IgE and 5q candidate region spanning interleukin-4 (IL-4) gene, we investigated whether detected by was linked IL-4 polymorphisms within were associated with levels. Both sib-pair method combined using regressive...