design, methodology, recruitment, data quality and study population

Background dsd-LIFE is a comprehensive cross-sectional clinical outcome study of individuals with disorders/differences of sex development (DSD). This study focuses on various rare genetic conditions characterized by impaired gonadal or adrenal functionality. Methods/Design The study aims to assess quality of life (QoL) as a measure of psychosocial adaptation, psychosexual and mental health aspects as major outcomes. Health status and functioning, medical and surgical therapies, participants’ views on health care, psychological and social support, sociodemographic factors and their interrelations will be investigated as factors associated with the outcomes. In addition, ethical considerations in the field of DSD are addressed and previous experiences with health care were gathered. One thousand and forty participants with different DSD conditions were recruited by 14 study centres in 6 European countries (France, Germany, the Netherlands, Poland, Sweden and the United Kingdom) from February 2014 until September 2015. The conditions included were: Turner syndrome (n = 301); 45,X0/46,XY conditions (n = 45); Klinefelter syndrome (n = 218); 47,XYY (n = 1); 46,XY gonadal dysgenesis/ovotestes (n = 63); complete androgen insensitivity (CAIS) (n = 71); partial androgen insensitivity (PAIS) (n = 35) and androgen synthesis disorders (n = 20); severe hypospadias (n = 25); other or non-classified 46,XY DSD (n = 8); 46,XX congenital adrenal hyperplasia (CAH) (n = 226); 46,XX gonadal dysgenesis/ovotestis (n = 21); and 46,XX in males (n = 6). For an add-on study, 121 46,XY male-assigned individuals with CAH due to 21-hydroxylase deficiency were recruited. Mean age of participants’ was 32.4 (+/− 13.6 years). Discussion Participation was high in conditions not commonly described as DSD, such as Turner and Klinefelter syndromes or CAH. Recruitment of individuals with XY DSD conditions proved to be more difficult. The data collection of PROs resulted in high data quality. Within medical and physical examination data, more missings and/or inaccurate data were found than expected. The European dsd-LIFE study recruited and evaluated the largest cross-sectional sample of individuals with different conditions classified under the term DSD. The data from this large sample will provide a sufficient basis for evidence-based recommendations for improvement of clinical care of individuals affected by a DSD condition. Trial registration German Clinical Trials Register DRKS00006072

Screening of MAMLD1 Mutations in 70 Children with 46,XY DSD: Identification and Functional Analysis of Two New Mutations

More than 50% of children with severe 46,XY disorders of sex development (DSD) do not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects in androgen biosynthesis, and abnormalities in androgen sensitivity, the Mastermind-like domain containing 1 (MAMLD1) gene, which was identified as critical for the development of male genitalia, may be implicated. The present study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and whether routine sequencing of MAMLD1 should be performed in these patients

Macrocephaly and developmental delay caused by missense variants in RAB5C

Rab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C. All but one patient with missense variants (n = 9) exhibited macrocephaly, combined with mild-to-moderate developmental delay. Patients with loss of function variants (n = 2) had an apparently more severe clinical phenotype with refractory epilepsy and intellectual disability but a normal head circumference. Four missense variants were investigated experimentally. In vitro biochemical studies revealed that all four variants were damaging, resulting in increased nucleotide exchange rate, attenuated responsivity to guanine exchange factors and heterogeneous effects on interactions with effector proteins. Studies in C. elegans confirmed that all four variants were damaging in vivo and showed defects in endocytic pathway function. The variant heterozygotes displayed phenotypes that were not observed in null heterozygotes, with two shown to be through a dominant negative mechanism. Expression of the human RAB5C variants in zebrafish embryos resulted in defective development, further underscoring the damaging effects of the RAB5C variants. Our combined bioinformatic, in vitro and in vivo experimental studies and clinical data support the association of RAB5C missense variants with a neurodevelopmental disorder characterized by macrocephaly and mild-to-moderate developmental delay through disruption of the endocytic pathway

Prise en charge des kystes ovariens fœtaux (étude prospective concernant le pronostic ovarien de 89 kystes à révélation anténatale)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Evaluation du retentissement vasculaire du syndrome des ovaires polykystiques chez l'adolescente pubère de moins de 20 ans

Le syndrome des ovaires polykystiques (SOPK) est associé à une dysfonction endothéliale précoce.Dans le but de rechercher sa présence dès l adolescence, nous avons réalisé une échographie vasculaire à un groupe d adolescentes SOPK (n=33) dont les mesures (IMT, Intima-Media Thickness, FMD, et Flow-Mediated Dilatation) ont été comparées à celles d un groupe témoin historique (n=19), chaque groupe ayant été réparti en obèses et non obèses. Une étude de corrélation a été réalisée entre ces paramètres vasculaires et les principales caractéristiques du SOPK. Aucune différence significative d IMT ni de FMD n a été mise en évidence ni aucune corrélation significative. En conclusion, les modifications vasculaires, même si elles sont précoces, ne semblent pas apparaître avant l âge adulte et sont probablement la conséquence du terrain métabolique associé au SOPK.TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Devenir à long terme des femmes prise en charge pour puberté précoce

Nous avons réalisé une enquête par questionnaire anonyme sur le devenir à long terme de 56 femmes traitées pour puberté précoce par analogues de LHRH. Cette population fut comparée à un groupe témoin. Nous n'avons pas mis en évidence de différence majeure concernant leur vie. Leur niveau d'études n'a pas été affecté par leur pathologie et elles n'ont pas de pratiques sexuelles particulièrement à risque. Par contre, ces femmes ont une plus forte propension au surpoids malgré une activité physique comparable aux témoins. Nous observons également un taux d'hyperandrogénie élevé à la fois sur le plan clinique et biologique. Les formes familiales représentent 30 % des cas.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Framework on Best Practice in environmental and other research in UK Overseas Territories

Part of the project From blue iguanas to blue vervain: sharing the colonial histories from the UK Overseas Territories aimed to develop a framework of best practice to enable increased prospects of resourcing for environmental work in the UK Overseas Territories (UKOTs) to address needs agreed by workers in the UKOTs. If these are adhered to both by those planning work and applying for funding and permissions and by the funding bodies, there are good prospects of moving towards a more equitable system. This framework was developed by consultations involving circulating drafts to bodies active in the UKOTs, followed by an online workshop on it on 25th July 2022 to confirm the document. This framework does not arise from nowhere. It builds on the recommendations and conclusions relating of improving equity in the access to funding already agreed by UKOT and Crown Dependencies practitioners (both NGO and governmental) at the online conference of the UK Overseas Territories Conservation Forum (UKOTCF) in March 2021, Staying Connected for Conservation in a Changed World (https://www.ukotcf.org.uk/onlineconference2021/), as well as from other conferences in the series, the experience of NGOs in the UKOTs themselves and researchers based around the world, and the Statement of 4th UK Overseas Territories and Crown Dependencies Environment Ministers’ Council Meeting, 28 – 29 April 2021 (https://www.ukotcf.org.uk/environment-ministers-council/fourth-meeting-2021/). Use of this framework will also help fulfil some of UK’s commitments under various international treaties, including the Convention on Biological Diversity, for example its Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity which aims at “sharing the benefits arising from the utilization of genetic resources in a fair and equitable way” (see https://www.gida-global.org/care). The framework follows the process of designing and delivering research, from the call for funding applications, through the involvement of partners, the development and consideration of applications, designing and undertaking the work, reporting it and ensuring access to the result. This Framework is available to be adopted by any organisation which wishes to strengthen equity in environmental work. See http://www.ukotcf.org.uk/framework-on-best-practice-in-environmental-and-other-research-in-uk-overseas-territories/Please reference as: Pienkowski, M; Wensink, C.M (2022). Framework on Best Practice in environmental and other research in UK Overseas Territories. UK Overseas Territories Conservation Forum. UKRI Grant reference AH/W008998/

Outil de dépistage de la puberté précoce chez la fille et le garçon en soins primaires

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Pathologies gynécologiques courantes chez la petite fille prépubère en médecine générale (enquête de pratiques auprès de 50 médecins généralistes des Hautes-Pyrénées)

Les médecins généralistes sont régulièrement confrontés à certaines pathologies gynécologiques chez les petites filles prépubères. Il n'existe pas de recommandations publiées par l'Afssaps sur le sujet. Nous avons réalisé une enquête de pratiques auprès de 50 médecins généralistes des Hautes-Pyrénées. Deux tiers des médecins estimaient avoir des connaissances insuffisantes dans ce domaine. Bien que globalement adaptée, la prise en charge des symptômes les plus fréquents (prurit vulvaire, brûlures mictionnelles, leucorrhées) pourrait être améliorée. Le lichen scléreux vulvaire était peu connu. Trop fréquemment en cas de vulvite, les médecins évoquaient une étiologie mycosique (80%). En cas de vaginite, 71% oubliaient de rechercher un éventuel corps étranger et 96% de donner un traitement anti-oxyure d'épreuve. Pour leur apporter une information complémentaire et tenter d'améliorer la qualité des soins primaires, nous avons mis au point un guide pratique sur les pathologies courantes.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prise en charge des vulvites et vulvovaginites chez les filles prépubères en médecine générale ( à propos de 47 situations cliniques rencontrées par les médecins généralistes maîtres de stage en gynécologie-pédiatrie ambulatoire en Midi-Pyrénées)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF