A5022007647- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Immune Response and Inflammation
- Urological Disorders and Treatments
- Hormonal and reproductive studies
- Neonatal Respiratory Health Research
- Prostate Cancer Treatment and Research
- Genetics and Neurodevelopmental Disorders
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Drug-Induced Hepatotoxicity and Protection
- PARP inhibition in cancer therapy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ion Transport and Channel Regulation
- Renal and related cancers
- Mitochondrial Function and Pathology
- Animal Disease Management and Epidemiology
- Hormonal Regulation and Hypertension
- Infant Nutrition and Health
- Endoplasmic Reticulum Stress and Disease
- Clinical Nutrition and Gastroenterology
- Sirtuins and Resveratrol in Medicine
- Nuclear Structure and Function
- Influenza Virus Research Studies
- Neuroscience of respiration and sleep
University Hospital of Bern
2019-2025
University of Bern
2007-2025
University Children’s Hospital Bern
2019-2020
BackgroundSteroidogenic factor 1 (SF-1/NR5A1) is essential for human sex development. Heterozygous NR5A1/SF-1 variants manifest with a broad range of phenotypes differences development (DSD), which remain unexplained.MethodsWe conducted retrospective analysis on the so far largest international cohort individuals variants, identified through I-DSD registry and research network.FindingsAmong 197 we confirmed diverse phenotypes. Over 70% 46, XY had severe DSD phenotype, while 90% XX...
Abstract Context Steroidogenic factor 1 (NR5A1/SF-1) is a nuclear receptor that regulates sex development, steroidogenesis, and reproduction. Genetic variants in NR5A1/SF-1 are common among differences of development (DSD) associate with wide range phenotypes, but their pathogenic mechanisms remain unclear. Objective Novel, likely disease-causing from the SF1next cohort individuals DSD were characterized to elucidate effect. Methods Different silico tools used predict impact novel on protein...
Oligogenic inheritance has been suggested as a possible mechanism to explain the broad phenotype observed in individuals with differences of sex development (DSD) harbouring NR5A1/SF-1 variants. We investigated genetic patterns oligogenicity cohort 30 variants and 46,XY DSD recruited from international SF1next study, using whole exome sequencing (WES) on family trios whenever available. WES data were analysed tailored filtering algorithm designed identify rare SF-1-related genes. Identified...
Resveratrol, a natural compound found in grapes, became very popular for its suggested protective effects against aging. It was reported to have similar positive on the human metabolism as caloric restriction. Recently, of resveratrol steroid biosynthesis cell systems and humans suffering from polycystic ovary syndrome also been reported, but exact mechanism this action remains unknown. Sirtuins seem targeted by mediate energy homeostasis. In study, we investigated mechanisms steroidogenesis...
Recognition of LPS depends on the interaction at least three molecules forming LPS-receptor complex. The most important ones, CD14, MD2 and Toll-like receptor (TLR) 4 share a high degree homology between species. In present study, we investigated importance species-specific restriction recognition using stably transfected HEK293 cell lines expressing either human or bovine complex components. Species-specific appeared to confer recognition, whereas CD14 only play minor role. addition LPS,...
Disorders/differences of sex development (DSD) are the result a discordance between chromosomal, gonadal and genital sex. DSD may be due to mutations in any genes involved determination general, as well and/or specifically. MAMLD1 is one recognized genes. However, its role controversial some variants present normal individuals, several have wild-type activity functional studies, Mamld1-knockout male mouse presents with genitalia reproduction. We previously tested 9 detected nine 46,XY...
The steroidogenic enzyme aromatase (CYP19A1) is required for estrogen biosynthesis from androgen precursors in the ovary and extragonadal tissues. role of aromatase, thus estrogens, best illustrated by genetic variations CYP19A1 gene leading to deficiency or excess.The objective this work characterize novel variants.Variants causing were suspected four 46,XX children African Indian origin careful clinical phenotyping. Sequencing identified variants. Minigene experiments, activity assay,...
Genetic defects affecting steroid biosynthesis cause cortisol deficiency and differences of sex development; among these are recessive mutations in the steroidogenic enzymes CYP11A1 CYP11B, whose function is supported by reducing equivalents donated ferredoxin reductase (FDXR) ferredoxin. So far, mitochondrial flavoprotein FDXR have been associated with a progressive neuropathic mitochondriopathy named FDXR-related (FRM), but insufficiency has not documented. However, patients FRM often...
Disorders of isolated mineralocorticoid deficiency, which cause potentially life-threatening salt-wasting crisis early in life, have been associated with gene variants aldosterone biosynthesis or resistance; however, some patients no such are found. WNT/β-catenin signaling is crucial for differentiation and maintenance the aldosterone-producing adrenal zona glomerulosa (zG). Herein, we describe a highly consanguineous family multiple perinatal deaths infants presenting at birth failure to...
NR5A1/ SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or be found in healthy carriers. The NR5A1 /SF-1 c.437G>C/p.Gly146Ala variant is common individuals with a DSD and has been suggested act as susceptibility factor for adrenal disease cryptorchidism. Since the allele frequency high general population, functional testing p.Gly146Ala revealed inconclusive results, disease-causing effect this questioned. However, role modifier still...
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Background Androgens are steroid hormones necessary for human sex development. Testosterone (T) and the more potent dihydrotestosterone (DHT) maybe best‐known androgens, which exert their effect by binding activating androgen receptor. The 5α reductases (SRD5As) catalyze conversion of T to DHT in classical production pathway, or from 17‐hydroxyprogesterone 17OH‐dihydroprogesterone, androstenedione androstanedione alternate pathways leading DHT. There two enzymes with differential expression,...