A5018333266- Sexual Differentiation and Disorders
- Hormonal and reproductive studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Urological Disorders and Treatments
- Genetic Syndromes and Imprinting
- Urologic and reproductive health conditions
- Genomics and Rare Diseases
- Congenital heart defects research
- Prostate Cancer Treatment and Research
- Parathyroid Disorders and Treatments
- Sperm and Testicular Function
- LGBTQ Health, Identity, and Policy
- Metabolism, Diabetes, and Cancer
- Diabetes Management and Research
- Genital Health and Disease
- Male Breast Health Studies
- Neuroendocrine Tumor Research Advances
- Growth Hormone and Insulin-like Growth Factors
- Genomic variations and chromosomal abnormalities
- Reproductive Biology and Fertility
- Hormonal Regulation and Hypertension
- Reproductive Health and Technologies
- Testicular diseases and treatments
- Metabolism and Genetic Disorders
- Diabetes and associated disorders
University of Lübeck
2016-2025
University Hospital Schleswig-Holstein
2015-2025
Klinik und Poliklinik für Kinder- und Jugendmedizin
2002-2024
Jena University Hospital
2024
Universitäres Kinderwunschzentrum Lübeck
2010-2023
University of Amsterdam
2022
Diabetes Australia
2015-2022
University of Pisa
2015
University of Glasgow
2013
Humboldt-Universität zu Berlin
2009-2012
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...
<i>Background:</i> In this epidemiological study, we sought to capture the incidence of ambiguous genitalia in neonates and describe initial management strategies. <i>Methods:</i> We used registry for rare diseases pediatrics Germany ascertain cases asked reporting institutions information on phenotype, laboratory tests, imaging results, diagnosis, sex assignment. <i>Results:</i> identified 80 within a 2-year study period calculated an 2 per 10,000 births...
Conversion of testosterone (T) to dihydrotestosterone (DHT) in genital tissue is catalysed by the enzyme 5α-reductase 2, which encoded SRD5A2 gene. The potent androgen DHT required for full masculinization external genitalia. Mutations gene inhibit activity, diminish formation, and hence cause defects varying degree. classical syndrome, formerly described as pseudovaginal perineoscrotal hypospadias, characterized a predominantly female phenotype at birth significant virtilization without...
Prenatal deficit of androgens or androgen action results in atypical genitalia individuals with XY disorders sex development (XY,DSD). XY,DSD include mainly gonadal and testosterone synthesis action. Previously, most were assigned to the female sex. Constructive genital surgery allowing heterosexual intercourse, gonadectomy, hormone therapy for feminization often performed. However, outcome studies are scarce.Our objective was evaluation satisfaction sexual life adults XY,DSD.We evaluated 57...
Context: Current immunoassays for analysis of plasma androgens in children have several limitations due to antibody-specific variations data and normal ranges. Mass spectrometry-based methods are available individual steroids but need complex sample preparation report only fragmentary reference the pediatric population. Objective: Our objective was develop a state art sensitive specific tandem mass spectrometry method high-throughput simultaneous determination concentrations androstenedione...
Several endocrine disorders that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). PHP type I, associated with blunted PTH-induced nephrogenous cAMP formation and phosphate excretion, is subdivided according presence or absence of additional abnormalities, Albright's hereditary osteodystrophy (AHO), reduced Gsalpha activity caused by GNAS mutations.We sought identify molecular defect in four unrelated patients who were thought have PHP-Ia because TSH mild AHO...
The focus of care in disorders sex development (DSD) is often directed to issues related and gender development. In addition, the molecular etiology remains unclear majority cases. To report range associated conditions identified international DSD (I-DSD) Registry. Anonymized data were extracted from I-DSD Registry for diagnosis, karyotype, rearing, genetic investigations, anomalies. If necessary, clarification was sought reporting clinician. Of 649 accessible cases, occurred 168 (26%); 103...
Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does study add? In some individuals with disorders sex development (DSD), gonadal tumour risk is increased. The individual estimated based molecular diagnosis age approaches 30% in high‐risk group. past, early gonadectomy has been advised for all 46XY DSD. Gonadectomy clearly represents an overtreatment many Thus, further clinical indicators are urgently needed. present provides a comprehensive...
It is unclear whether the proportion of infants with a disorder sex development who are raised as male or female has changed over time. The temporal trends in assignment affected cases entered International Disorder Sex Development (I-DSD) Registry were studied.Cases disorders reported partial androgen insensitivity syndrome (PAIS; n = 118), gonadal (DGD; 232), and synthesis (DAS; 104) divided into those born before 1990, 1990-1999, after 1999. External appearance genitalia was described by...
In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in receptor gene (AR) is lacking. To assess clinical characteristics and outcomes young men PAIS relation to results AR analysis. Through International Disorders Sex Development Registry, information was gathered on having (n = 52) who presented before age 16 years had genetic analysis AR. The median ages at presentation time study...
<h3>Background</h3> <i>SOX9</i> mutations cause the skeletal malformation syndrome campomelic dysplasia in combination with XY sex reversal. Studies mice indicate that SOX9 acts as a testis-inducing transcription factor downstream of <i>SRY</i>, triggering Sertoli cell and testis differentiation. An SRY-dependent testis-specific enhancer for <i>Sox9</i> has been identified only mice. A previous study implicated copy number variations (CNVs) 78 kb region 517–595 upstream aetiology both 46,XY...
Abstract Context Standardized description of external genitalia is needed in the assessment children with atypical genitalia. Objectives To validate External Genitalia Score (EGS), to present reference values for preterm and term babies up 24 months correlate obtained scores anogenital distances (AGDs). Design, Setting A European multicenter (n = 8) validation study was conducted from July 2016 2018. Patients Methods EGS based on masculinization score but uses a gradual scale female male...
Abstract Objective 17β-Hydroxysteroid dehydrogenase 3 deficiency (17β-HSDD) and 5α-reductase type 2 (5α-RD) are rare 46,XY differences of sex development (DSD). This study aims to enlarge the limited knowledge on long-term gonadal function pathology in these conditions. Design Retrospective multicentre cohort study. Methods Data phenotype, laboratory results, hormone treatment were collected from patients aged ≥16 years at time data collection with genetically confirmed 17β-HSDD 5α-RD 10...
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...
Abstract Background 46,XY gonadal dysgenesis is classified as complete (CGD) or partial (PGD) subtypes. The phenotype of PGD and the long-term outcome not clearly defined. Objective To evaluate clinical features pubertal in a large cohort, using CGD comparator for diagnostic clarity. Methods Patients with GD were identified from I-DSD Registry data on phenotype, genetics, biochemistry, histology development collated three categories; (n=100), assigned female (PGDf, n=107) male (PGDm, n=103)...
Abnormal human spermatogenesis is caused by a variety of genetic and acquired conditions. Because dependent on androgens, some males may have minimal form androgen insensitivity that does not inhibit virilization but impairs fertility. This has lead us to investigate the possibility abnormalities in receptor (AR) gene large cohort suffering from infertility unknown cause. We studied 180 with variable impairment spermatogenesis. In all patients, serum levels testosterone gonadotropins were...
Background. The distinction of sporadic from inherited medullary thyroid carcinomas (MTCs) is clinical importance because the differences in prognosis, and need for family screening genetic counseling required latter. Germline mutations RET protooncogene are associated with multiple endocrine neoplasia (MEN) type 2A, familial carcinoma (FMTC), MEN 2B. Somatic point same gene have been identified a subset sporadically occurring carcinomas. Methods. A nonisotopic polymerase chain...
Abstract Disruption of the P450 side-chain cleavage cytochrome (P450scc) enzyme due to deleterious mutations CYP11A1 gene is thought be incompatible with fetal survival because impaired progesterone production by fetoplacental unit. We present a 46,XY patient homozygous disruption CYP11A1. The child was born prematurely complete sex reversal and severe adrenal insufficiency. Laboratory data showed diminished or absent steroidogenesis in all pathways. Molecular genetic analysis revealed...