Disorders of Sex Development: Platform for Basic and Translational Research

性发育障碍：基础和转化研究平台

基本信息

批准号：
8708527
负责人：
DAVID Eric. SANDBERG
金额：
$ 81.46万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-26 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8708527
关键词：
Accounting Advocate Affect Algorithms Anatomy Appearance Basic Science Biochemical Biological Biology Birth Candidate Disease Gene Child Clinical Clinical Management Clinical Research Clitoris Consensus Cryptorchidism DNA Data Decision Making Development Diagnosis Diagnostic Effectiveness Emotional Ensure Environment Equilibrium Europe European Union Evaluation Family Female Fertility Financial Support Fostering Foundations Functional disorder Future Gender Genetic Genital system Genotype Goals Guidelines Health Health Personnel Health Professional Healthcare Healthcare Systems Human Hypertrophy Hypospadias Incidence Information Technology Interdisciplinary Study Investigation Knowledge Leadership Learning Left Link Longevity Longitudinal Studies Measures Medical Medical Care Team Medical Genetics Minor Molecular Diagnosis North America Operative Surgical Procedures Outcome Parents Pathology Pathway interactions Patient Care Patients Persons Phenotype Physiological Population Positioning Attribute Procedures Process Protocols documentation Proxy Quality of life Quality-of-Life Assessment Recommendation Records Registries Reporting Research Research Design Research Infrastructure Research Personnel Resources Sampling Scientist Sequence Analysis Sexual Development Sexual Dysfunction Site Standardization Time Translational Research Translations Treatment Protocols Uncertainty Uterus Variant base behavioral health cancer risk clinical care clinical practice design evidence base experience health care delivery health related quality of life improved indexing insight male malformation multidisciplinary novel patient registry prospective psychologic psychosocial research and development sex sex development disorder skills social success tool

项目摘要

DESCRIPTION (provided by applicant): Disorders of sex development (DSD) are phenotypically heterogeneous, ranging from minor genital malformations (hypospadias, cryptorchidism, hypertrophy of the clitoris) to genital ambiguity. In the aggregate, DSD have an estimated incidence of about 1%. DSD can result in severe consequences for behavioral health, fertility, cancer risk and quality of life. For families, the birth of a child with a DSD, and the accompanying uncertainty about future psychological and sexual development, is believed to be extraordinarily stressful. Recently, the debate over clinical management of DSD, in particular gender assignment and genital surgery, has intensified; yet the scientific data on patient outcomes have remained very incomplete. Major obstacles to optimal clinical management of DSD include gaps in understanding of pathophysiology, impeding precise diagnostic categorization, along with the absence of prospective longitudinal studies of health and quality of life outcomes. This proposal delivers a platform for hypothesis-based research on the mechanisms of sex development and evidence-based care for patients and families affected by DSD. Aim 1 identifies novel genetic mechanisms of sex development and improves understanding of the pathophysiology and molecular diagnosis of DSD by a step-wise approach of specific DNA capture and sequencing, analysis of copy number variants, and identification of novel candidate genes for DSD. Aim 2 delivers standardized tools for reliable phenotypic descriptions across multiple study sites and investigators, including radiological, biochemical, histological evaluations and descriptions of genital phenotype and post- surgical appearance and function, facilitating interpretation of genetic, gender, and quality of life outcomes Aim 3 identifies short and medium-term outcomes by delivering a comprehensive psychosocial and health-related quality of life assessment battery using psychometrically robust measures suitable for use in routine clinical care, a necessary step leading to evidence-based psychosocial treatment protocols. Aim 4 builds a sustainable research infrastructure and ensures rapid translation of new evidence into ongoing clinical practice by integrating standardized DSD diagnostic and treatment protocols and fostering the transfer of best practices in healthcare delivery across network sites. This registry provides the analytic platform by which data are collected, analyzed, and shared among researchers and sites, while a collaborative network will supply the foundation for multidisciplinary basic, clinical, and translational research. This unique combination of genetic, phenotypic and psychosocial approaches will transform participating sites into self-sustaining DSD "centers of excellence" for clinical care along with the added value of a registry serving as a critical resource for hypothesis-driven research.

描述（由申请人提供）：性发育的疾病（DSD）在表型上是异质性的，从较小的生殖器畸形（Hypospadias，cryptorchidism，Clitoris的肥大）到生殖器歧义。在总体中，DSD的估计发病率约为1％。 DSD可能会对行为健康，生育，癌症风险和生活质量造成严重影响。对于家庭而言，据信，患有DSD的孩子的诞生以及对未来心理和性发展的不确定性的伴随不确定性，被认为是极大的压力。最近，关于DSD临床管理的辩论，尤其是性别分配和生殖器手术，已经加强了。然而，有关患者结局的科学数据仍然非常不完整。 DSD最佳临床管理的主要障碍包括了解病理生理学的差距，阻碍精确的诊断分类，以及缺乏对健康和生活质量结果的前瞻性纵向研究。该建议为基于假设的研究提供了一个平台，该研究对受DSD影响的患者和家庭的性发展机制和循证护理机制提供了平台。 AIM 1通过特定DNA捕获和测序的逐步方法，拷贝数变异的分析以及鉴定DSD的新型候选基因的逐步方法来确定性发展的新遗传机制，并提高对DSD的病理生理学和分子诊断DSD的理解。 AIM 2提供标准化工具，用于在多个研究站点和研究人员之间进行可靠的表型描述，包括放射学，生物化学，组织学评估以及生殖器表型和外科手术后外观和功能的描述，并促进对遗传，性别和中等范围的质量来评估生活的质量和中等范围的质量，以促进生活的质量和中等程度的效果。在心理方面的鲁棒措施适用于常规临床护理，这是导致基于证据的社会心理治疗方案的必要步骤。 AIM 4建立了可持续的研究基础设施，并通过整合标准化的DSD诊断和治疗方案并促进了跨网络地点的医疗保健提供中最佳实践的转移，从而确保将新证据快速转化为正在进行的临床实践。该注册表提供了一个分析平台，在研究人员和网站之间收集，分析和共享数据，而协作网络将为多学科基本，临床和转化研究提供基础。这种遗传，表型和社会心理方法的独特组合将使参与站点成为自我维持的DSD“卓越中心”，以进行临床护理，以及注册表的附加值，作为假设驱动研究的关键资源。