Barseghyan H, Délot E, Vilain E
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Horm Metab Res. 2015 May;47(5):312-20. doi: 10.1055/s-0035-1548831. Epub 2015 May 13.
The Chicago Consensus Conference of 2005 defined Disorders of Sex Development (DSD) as "congenital conditions in which the development of chromosomal, gonadal or anatomic sex is atypical." DSD diagnoses are difficult to establish. A lack of standardization of anatomical and endocrine phenotyping and the limited number of known DSD genes and genotype/correlation has long hampered the field, leaving many patients without a definitive diagnosis. The resulting uncertainty may intrinsically pose a great amount of discomfort to affected individuals and their families. DSD-causative genes have historically been identified thanks to positional cloning of disease-associated variants segregating in families or chromosomal rearrangements. Recent advances of chromosomal microarray and exome sequencing technologies are allowing for higher rates of diagnostic success for DSD patients and are changing clinical practice. In this review, we discuss the application of these technologies and their findings as an upcoming model for clinical diagnosis of DSD. We show that exome sequencing is a valuable tool and we propose that it should be used as a first-stage diagnostic technique because it allows for early identification of a genetic cause that may be critical for patient management.
2005年芝加哥共识会议将性发育障碍（DSD）定义为“染色体、性腺或解剖学性别发育异常的先天性疾病”。DSD的诊断很难确立。解剖学和内分泌表型缺乏标准化，以及已知的DSD基因数量有限和基因型/相关性有限，长期以来一直阻碍着该领域的发展，导致许多患者无法得到明确诊断。由此产生的不确定性可能会给受影响的个体及其家庭带来极大的不适。历史上，DSD致病基因是通过对家族中分离的疾病相关变异或染色体重排进行定位克隆而确定的。染色体微阵列和外显子组测序技术的最新进展使DSD患者的诊断成功率更高，并正在改变临床实践。在本综述中，我们讨论了这些技术的应用及其发现，将其作为即将到来的DSD临床诊断模型。我们表明外显子组测序是一种有价值的工具，并建议将其用作第一阶段诊断技术，因为它可以早期识别可能对患者管理至关重要的遗传原因。
