Biocruces Bizkaia Health Research Institute, Cruces University Hospital, UPV/EHU, CIBERER, CIBERDEM, ENDO-ERN. Plaza de Cruces 12, 48903 Barakaldo, Spain.
Department of Pediatrics, Endocrinology Section, Ain Shams University, 38 Abbasia, Nour Mosque, El-Mohamady, Al Waili, Cairo 11591, Egypt.
Int J Mol Sci. 2020 Nov 13;21(22):8554. doi: 10.3390/ijms21228554.
Variants of are often found in individuals with 46,XY disorders of sex development (DSD) and manifest with a very broad spectrum of clinical characteristics and variable sex hormone levels. Such complex phenotypic expression can be due to the inheritance of additional genetic hits in DSD-associated genes that modify sex determination, differentiation and organ function in patients with heterozygous variants. Here we describe the clinical, biochemical and genetic features of a series of seven patients harboring monoallelic variants in the gene. We tested the transactivation activity of novel variants. We additionally included six of these patients in a targeted diagnostic gene panel for DSD and identified a second genetic hit in known DSD-causing genes , and in three individuals. Our study increases the number of variants related to 46,XY DSD and supports the hypothesis that a digenic mode of inheritance may contribute towards the broad spectrum of phenotypes observed in individuals with a heterozygous variation.
常染色体显性遗传疾病 46,XY 性别发育障碍（DSD）患者中存在 基因的变异，这些变异表现出非常广泛的临床特征和可变的性激素水平。这种复杂的表型表达可能是由于在 DSD 相关基因中遗传了额外的遗传打击，这些基因改变了杂合子 变异患者的性别决定、分化和器官功能。在这里，我们描述了一系列携带 基因单等位基因变异的 7 名患者的临床、生化和遗传特征。我们测试了新型 变异的转录激活活性。此外，我们将其中 6 名患者纳入 DSD 的靶向诊断基因面板，并在 3 名个体中鉴定出第二个遗传打击，位于已知的 DSD 致病基因 、 和 中。我们的研究增加了与 46,XY DSD 相关的 基因变异数量，并支持这样一种假说，即双基因遗传模式可能导致携带杂合 变异的个体表现出广泛的表型。
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