A5047403231- Hypothalamic control of reproductive hormones
- Pituitary Gland Disorders and Treatments
- Hormonal Regulation and Hypertension
- Sexual Differentiation and Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Growth Hormone and Insulin-like Growth Factors
- Adrenal Hormones and Disorders
- Adrenal and Paraganglionic Tumors
- Ovarian function and disorders
- Plant Reproductive Biology
- Estrogen and related hormone effects
- Pediatric Hepatobiliary Diseases and Treatments
- Renal and related cancers
- Genetic Syndromes and Imprinting
- Hormonal and reproductive studies
- Neuroblastoma Research and Treatments
- Gallbladder and Bile Duct Disorders
- Prenatal Screening and Diagnostics
- Ovarian cancer diagnosis and treatment
- Receptor Mechanisms and Signaling
- Cancer, Hypoxia, and Metabolism
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Genomics and Rare Diseases
- Liver Disease and Transplantation
Bicêtre Hospital
2016-2025
Université Paris-Saclay
2007-2024
Assistance Publique – Hôpitaux de Paris
2015-2024
Inserm
2015-2024
Hôpital Antoine-Béclère
2013-2024
Physiologie et Physiopathlogie Endocriniennes
2013-2023
Toxicologie, Pharmacologie et Signalisation Cellulaire
2018-2022
Université Paris-Sud
2010-2019
Hôpitaux Universitaires Paris-Ouest
2014-2019
Hôpital Cochin
2017
We investigated whether mutations in the gene encoding gonadotropin-releasing hormone 1 (GNRH1) might be responsible for idiopathic hypogonadotropic hypogonadism (IHH) humans. identified a homozygous GNRH1 frameshift mutation, an insertion of adenine at nucleotide position 18 (c.18-19insA), sequence N-terminal region signal peptide-containing protein precursor (prepro-GnRH) teenage brother and sister, who had normosmic IHH. Their unaffected parents sibling was tested were heterozygous. This...
Context: Missense loss-of-function mutations in TAC3 and TACR3, the genes encoding neurokinin B its receptor NK3R, respectively, were recently discovered kindreds with nonsyndromic normosmic congenital hypogonadotropic hypogonadism (CHH), thus identifying a fundamental role of this pathway human gonadotrope axis. Objective: The objective study was to investigate consequences on axis deletion TACR3 truncation adult patients complete CHH. Results: We identified three unrelated same homozygous...
Germline mutations of the AIP (aryl-hydrocarbon receptor interacting protein) gene are associated with a predisposition to pituitary adenomas. Such found in about half patients familial acromegaly, but penetrance is incomplete.We studied prevalence germline large cohort apparently sporadic adenomas.A total 443 adenomas all histotypes, who had no history or multiple endocrine neoplasia and were examined at Bicêtre University Hospital, tertiary referral center, between 2007 2010, enrolled this...
Pulsatile gonadotropin-releasing hormone (GnRH) is crucial to normal reproductive function and abnormalities in pulse frequency give rise dysfunction. Kisspeptin neurokinin B (NKB), neuropeptides secreted by the same neuronal population ventral hypothalamus, have emerged recently as critical central regulators of GnRH thus gonadotropin secretion. Patients with mutations resulting loss signaling either these neuroendocrine peptides fail advance through puberty but mechanisms mediating this...
BACKGROUNDKallmann syndrome (KS) is a genetic disorder associating pubertal failure with congenitally absent or impaired sense of smell. KS related to defective neuronal development affecting both the migration olfactory nerve endings and GnRH neurons. The discovery several mutations responsible for led identification signaling pathways involved in these processes, but so far identified account only 30% cases KS. Here, we attempted identify new genes by using pan-genomic approach.
Mouse splenic marginal zone precursors (MZPs) differentiate into B (MZB) cells under a signaling pathway involving Notch2 and its ligand, delta-like 1 ligand (Dll1). We report the identification of an MZP subset in spleen young children. These MZPs MZ-like vitro presence OP9 expressing human DLL1, as demonstrated by up-regulation classical MZB cell markers. A set diagnostic genes discriminating IgM+IgD+CD27+ blood from switched was identified (up-regulation SOX7, down-regulation TOX, COCH,...
Mouse splenic marginal zone precursors (MZPs) differentiate into B (MZB) cells under a signaling pathway involving Notch2 and its ligand, delta-like 1 ligand (Dll1). We report the identification of an MZP subset in spleen young children. These MZPs MZ-like vitro presence OP9 expressing human DLL1, as demonstrated by up-regulation classical MZB cell markers. A set diagnostic genes discriminating IgM(+)IgD(+)CD27(+) blood from switched was identified (up-regulation SOX7, down-regulation TOX,...
Background and Aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, real‐world lacking. This study aimed to elucidate the natural history of liver disease in contemporary, international cohort children with ALGS. Approach Results: was multicenter retrospective clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 August 2019. Native survival (NLS) event‐free rates...
Context TAC3/TACR3 mutations have been reported in normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). In the absence of animal models, studies human neuroendocrine phenotypes associated with neurokinin B and NK3R receptor dysfunction can help to decipher pathophysiology this signaling pathway. Objective To evaluate prevalence mutations, characterize novel TACR3 analyze profiles nCHH caused by deleterious biallelic mutations. Results From a cohort 352 CHH, we selected...
Pituitary adenomas are rare in children and adolescents. The response of macroprolactinomas to dopamine agonists (DA) this age group has been less extensively studied than adults.We retrospectively analyzed data on a large cohort young patients with macroprolactinomas.Patients aged younger 20 years at macroprolactinoma diagnosis seen three tertiary referral centers between 1983 2013 were by analyzing their clinical genetic (AIP MEN1) characteristics. Hormonal tumoral responses DA analyzed,...
Pituitary stalk interruption represents a frequent feature of congenital hypopituitarism, but only rare cases have been assigned to known genetic cause.Using candidate gene approach, we tested several genes as potential causes hypopituitarism with pituitary interruption. We hypothesized that ectopic posterior may be consequence defective neuronal axon projections along the or angiogenesis hypophyseal portal circulation. Considering role prokineticin 2 pathway in and migration, screened PROK2...
Aldosterone exerts its effects mainly by activating the mineralocorticoid receptor (MR), a transcription factor that regulates gene expression through complex and dynamic interactions with coregulators transcriptional machinery, leading to fine-tuned control of vectorial ionic transport in distal nephron. To identify genome-wide aldosterone-regulated MR targets human renal cells, we set up chromatin immunoprecipitation (ChIP) assay using specific anti-MR antibody differentiated cell line...
Background Arthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the diagnosis rates of AMC, evaluate added value whole exome sequencing (WES) compared with targeted (TES) identify new genes 315 unrelated undiagnosed families. Methods Several genomic approaches used including mapping disease loci consanguineous families, TES then WES. Sanger was...
Background and Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, approved pharmacologic therapy for cholestatic in ALGS. Since long-term placebo-controlled studies are not feasible or ethical children rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials aligned harmonized natural history cohort the G lobal AL agille A lliance...
Abstract Importance A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% patients with acromegaly and related to the ectopic expression glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) somatotropinomas. Recently, we identified germline pathogenic variants somatic loss heterozygosity lysine demethylase 1A (KDM1A) GIP-dependent primary bilateral macronodular adrenal hyperplasia Cushing's syndrome. The GIPR both pituitary lesions...
Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related not sufficient. Non-identical twin females presented adolescents to emergency department severe progressive headache caused by large macroadenomas require neurosurgery; one patient had incipient apoplexy. Post-surgically, patients were found have silent somatotrope...
Primary ovarian insufficiency (POI) is a major cause of anovulation and infertility in women. This disease affects 1% women before 40 years, several genetic causes have been reported.The aim the study was to evaluate prevalence NOBOX mutations new large cohort with POI characterize these variants identify novel target gene.A total 213 unrelated patients were screened for mutations, luciferase reporter assays performed identified.We reported 3 2 recurrent heterozygous missense rare found 12...
What is the exact prevalence of Kisspeptin Receptor (KISS1R) mutations in population patients with normosmic congenital hypogonadotrophic hypogonadism (nCHH) by comparison other genes, involved gonadotrophin-releasing hormone (GnRH) release or action? KISS1R mutants are responsible for nCHH phenotype only a small minority cases and were less prevalent than GnRH (GNRHR) mutations. The respective each genetic causes unclear. Large series very rare suffer from heterogeneity CHH studied....