Growth and Development Research Unit, Vall d’Hebron Research Institute (VHIR), Center for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
Eur J Endocrinol. 2018 Oct 1;179(4):R197-R206. doi: 10.1530/EJE-18-0256.
The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 ‘DSDnet’ was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.
性别发育差异或障碍（DSD）的鉴别诊断属于医学中最复杂的领域之一。它需要一个多学科团队，采用综合和互补的方法，包括彻底的临床、激素和遗传评估。这份由欧盟科学技术合作组织（COST）BM1303 号行动“DSDnet”撰写的立场文件由该领域的领先专家撰写，重点介绍了 DSD 患者遗传诊断的当前最佳实践。核型确定是三个主要诊断 DSD 子类之一，因此是强制性的初始步骤。随后，进一步的分析包括单基因 DSD 病因的分子研究或拷贝数变异（CNV）分析或两者兼而有之。候选基因面板提供快速可靠的结果。全外显子组和全基因组测序（WES 和 WGS）是有价值的方法学进展，目前正在从基础科学向 DSD 领域的临床常规服务过渡。然而，除了涵盖已知的 DSD 候选基因外，WES 和 WGS 还有助于识别 DSD 的新的遗传原因。在每个 DSD 病例中，诊断解释必须非常谨慎地进行，并需要仔细的科学验证。
