Kalinchenko N Y, Tiulpakov A N
Endocrinology Research Center.
Probl Endokrinol (Mosk). 2020 Dec 12;66(6):59-64. doi: 10.14341/probl12695.
Disorders of sex development (DSDs) are congenital conditions in which phenotype does not correspond to chromosomal and gonadal sex. To date, the etiology of DSD is established only in half of the cases. With the development of modern methods of molecular genetic diagnostics in the last decade, a number of new regulators of gonad differentiation have been discovered, whose expression disorders can lead to DSD. Among these factors, Mitogen-activated triple protein kinase 1 (MAP3K1). A distinctive feature of studying the detected variants in the MAP3K1 gene that they lead to activation of MAP3K1. It does not allow using generally accepted pathogenicity assessment algorithms. However, the frequency of detection of changes in MAP3K1 is up to 18% of all cases of DSD, according to literature, which emphasizes the importance of studying each identified case, establishing the relationship of the disease with the identified genetic disorders. In this article, we present a clinical, hormonal, and molecular genetic description of 7 cases of DSD associated with variants in MAP3K1, an analysis of the significance of our own data, and a short analysis of the current scientific literature on this issue.
性发育障碍（DSD）是一种先天性疾病，其表型与染色体和性腺性别不相符。迄今为止，仅在半数病例中确定了DSD的病因。在过去十年中，随着现代分子遗传学诊断方法的发展，已发现许多性腺分化的新调节因子，其表达紊乱可导致DSD。在这些因素中，有丝分裂原激活的三联蛋白激酶1（MAP3K1）。研究MAP3K1基因中检测到的变异体的一个显著特征是它们会导致MAP3K1的激活。这使得无法使用普遍接受的致病性评估算法。然而，根据文献，MAP3K1变化的检测频率在所有DSD病例中高达18%，这强调了研究每一例确诊病例、确定疾病与已确定的遗传紊乱之间关系的重要性。在本文中，我们介绍了7例与MAP3K1变异相关的DSD病例的临床、激素和分子遗传学描述，分析了我们自己数据的意义，并对关于这个问题的当前科学文献进行了简要分析。
