性别发育差异（DSD）遗传学的最新进展。

Update on the genetics of differences of sex development (DSD).

机构信息

Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium; Division of Pediatric Endocrinology, Department of Internal Medicine and Pediatrics, Ghent University Hospital and Ghent University, Ghent, Belgium.

Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.

出版信息

Best Pract Res Clin Endocrinol Metab. 2019 Jun;33(3):101271. doi: 10.1016/j.beem.2019.04.005. Epub 2019 Apr 13.

DOI:10.1016/j.beem.2019.04.005

PMID:31005504

Abstract

Human gonadal development is regulated by the temporospatial expression of many different genes with critical dosage effects. Subsequent sex steroid hormone production requires several consecutive enzymatic steps and functional hormone receptors. Disruption of this complex process can result in atypical sex development and lead to conditions referred to as differences (disorders) of sex development (DSD). With the advent of massively parallel sequencing technologies, in silico protein modeling and innovative tools for the generation of animal models, new genes and pathways have been implicated in the pathogenesis of these conditions. Here, we provide an overview of the currently known DSD genes and mechanisms involved in the process of gonadal and phenotypical sex development and highlight phenotypic findings that may trigger further diagnostic investigations.

摘要

人类性腺的发育受到许多不同基因在时空表达上的调控，这些基因具有关键的剂量效应。随后的性激素产生需要几个连续的酶步骤和功能性激素受体。这个复杂过程的破坏可能导致非典型的性发育，并导致被称为性发育差异（障碍）（DSD）的情况。随着大规模平行测序技术、计算机蛋白质建模和用于生成动物模型的创新工具的出现，新的基因和途径已被牵连到这些情况的发病机制中。在这里，我们提供了一个概述，介绍了目前已知的 DSD 基因和机制，以及参与性腺和表型性别发育的过程，并强调了可能引发进一步诊断研究的表型发现。