Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Pediatric Endocrinology, Hospital Universitario San Ignacio, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Mol Med Rep. 2020 Jan;21(1):97-106. doi: 10.3892/mmr.2019.10819. Epub 2019 Nov 12.
Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as 'other' since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad‑spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations.
性发育障碍（DSD）是一种先天性疾病，其个体的外部表现与染色体组成或性腺性别不一致。换句话说，在解剖性别男性和女性表型之间存在一种模糊或中间状态。这些非典型情况表现为多种方式，从生殖器模糊到表现如此减弱以至于可能未被注意到或看起来正常。目前，对于导致这些结果的因素缺乏了解；然而，它们很可能是由产前和产后发育过程中的遗传、激素和环境因素决定的。本研究通过常规细胞遗传学分析、FISH 和 MLPA（用于 SF1、DAX1、SOX9、SRY 和 WNT4）确定了哥伦比亚患者 DSD 的遗传病因。本研究使用了一组 43 名具有性发育障碍临床表型的患者。使用这种多步骤实验方法，获得了 25.58%的诊断百分比：17 名患者（39.53%）被归类为性腺发育障碍，其中大多数为卵巢睾丸发育障碍，存在性染色体的数目和/或结构改变，9 名患者（20.93%）被归类为 46，XY 核型的睾丸 DSD，3 名患者（6.98%）被归类为 46，XX 核型的卵巢 DSD。其余 14 名患者（32.56%）被归类为“其他”，因为他们无法归入特定的性腺发育类别，对应于尿道下裂和多种先天性异常。这些发现强调了在性腺活检中进行组织学和细胞遗传学研究的重要性。在 43 例患者中，有 11 例患者通过本研究中提出的多步骤实验方案获得了病因学或组织学发现，这些发现可用于确定 DSD 患者的医疗管理。总之，对于 DSD 的病因诊断，需要采用广泛的方法，包括内分泌测试、常规核型分析、FISH 进行分子核型分析以及分子测试，此外还需要进行性腺组织分析，以确定遗传改变。
