A5031441859- Sexual Differentiation and Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Urological Disorders and Treatments
- Hormonal and reproductive studies
- Hormonal Regulation and Hypertension
- Reproductive Biology and Fertility
- Estrogen and related hormone effects
- Sperm and Testicular Function
- Diabetes and associated disorders
- Animal Genetics and Reproduction
- Pluripotent Stem Cells Research
- Adrenal Hormones and Disorders
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Metabolism and Genetic Disorders
- Pharmacogenetics and Drug Metabolism
- Epigenetics and DNA Methylation
- Growth Hormone and Insulin-like Growth Factors
- Aldose Reductase and Taurine
- Adolescent Sexual and Reproductive Health
- Diabetes Management and Research
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Testicular diseases and treatments
University of Fribourg
2015-2024
University Children's Hospital Zurich
2004-2017
Boston Children's Hospital
2001-2011
Hôpital Jeanne de Flandre
2011
Centre Hospitalier Universitaire de Lille
2011
Swiss Integrative Center for Human Health
2009
Temple Street Children's University Hospital
2006
University of Zurich
1998-2000
Center for Pediatric Endocrinology Zurich
1997
WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals. An 18-year-old woman presented with primary amenorrhea and an absence müllerian-derived structures, unilateral renal agenesis, clinical signs excess--a phenotype resembling Mayer-Rokitansky-Küster-Hauser syndrome remarkably similar Wnt4-knockout mice. A genetic evaluation revealed loss-of-function mutation WNT4 gene. appears be important...
The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations the WNT4 gene appear cause developmental abnormalities of differentiation women and mice. We recruited six patients with different degrees Müllerian abnormalities, or without renal aberrations a normal 46,XX karyotype. A clear androgen excess was found only one patient. This 19-year-old woman affected by primary amenorrhoea, absence ducts derivatives, clinical (acne hirsutism)...
Müllerian duct development depends on gene and hormone interactions. Female Wnt4-knockout mice lack müllerian ducts are virilized due to the inappropriate expression of enzymes required for androgen production (normally repressed in female ovary). The WNT4 mutation was recently reported be associated with failure formation virilization two 46, XX women.This collaborative work designed determine whether could identified a group adolescent girls Mayer-Rokitansky-Küster-Hauser syndrome.We...
The mechanism by which the β-cell transcription factor Pax4 influences cell function/mass was studied in rat and human islets of Langerhans. transcripts were detected adult islets, levels induced mitogens activin A betacellulin. Wortmannin suppressed betacellulin-induced expression, implicating phosphatidylinositol 3-kinase signaling pathway. Adenoviral overexpression caused a 3.5-fold increase proliferation with concomitant 1.9-, 4-, 5-fold Bcl-xL (antiapoptotic), c-myc, Id2 mRNA levels,...
Abstract Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex [DSD]), yet the exact rank function human CBX2 this pathway remains unclear. Here, we performed large-scale mapping analysis vivo target loci protein Sertoli-like NT-2D1 cells, using DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation selected candidate genes qRT-PCR...
Context: Cortisone reductase deficiency (CRD) is characterized by a failure to regenerate cortisol from cortisone via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), resulting in increased clearance, activation of the hypothalamic-pituitary-axis (HPA) and ACTH-mediated adrenal androgen excess. 11β-HSD1 oxoreductase activity requires reduced nicotinamide adenine dinucleotide phosphate-generating enzyme hexose-6-phosphate (H6PDH) within endoplasmic reticulum. CRD manifests with...
Context: The characteristics of P450c17 deficiency include 46,XY disorder sex development, hypertension, hypokalemia, and lack pubertal development.
Abstract Context Estrogen resistance due to mutations in the estrogen receptor α gene (ESR1) has been described men and women is characterized by osteoporosis, delayed bone age continuous growth adulthood, puberty multiple ovarian cysts women. Although β ESR2 were found 46, XY patients with differences of sex development, no genetic variants linked gonadal defects Settings Patient Here we describe a 16-year-old female patient who came our tertiary care hospital complete lack action, as...
Wolcott-Rallison syndrome (WRS) is an autosomal recessive disorder characterized by neonatal or early infancy type 1 diabetes, epiphyseal dysplasia, and growth retardation. Mutations in the EIF2AK3 gene, encoding eukaryotic initiation factor 2α-kinase 3 (EIF2AK3), have been found WRS patients. Here we describe a girl who came to our attention at 2 months of age with severe hypertonic dehydration diabetic ketoacidosis. A diagnosis diabetes was made insulin treatment initiated. Growth...
Sertoli cells are main players in the male gonads development and their study may shed light on 46,XY disorders of sex development. Mature primary incapable proliferating prolonged vitro cultures available cell models have several limitations since they derive from mouse or human cancer tissues. We differentiated fibroblasts-derived induced pluripotent stem into Sertoli-like and, order to characterize this new model, we performed gene expression analyses by generation sequencing techniques....
The molecular basis of isolated 17,20-lyase deficiency was clarified in a newborn male patient from Israel with micropenis, undescended testes, and hormonal pattern consistent deficiency. Analysis the CYP17 gene revealed presence compound heterozygosity. One allele carries single base pair deletion (T at position 198 exon 1) leading to frame shift introduction premature stop codon, TGA, residue 74 place Val. other bears missense mutation due change, T G, which substitutes Phe417 Cys. proof...