Federal State Budgetary Institution "Centre for Strategic Planning and Management of Biomedical Health Risks" of the Federal Medical Biological Agency (Centre for Strategic Planning of FMBA of Russia), Moscow, Russia.
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Moscow, Russia.
PeerJ. 2024 Nov 4;12:e18243. doi: 10.7717/peerj.18243. eCollection 2024.
Nearly identical, repetitive elements in the genome contribute to the variability in genetic inheritance patterns, particularly in regions like the RCCX locus, where such repeats can lead to structural variations. In addition, during the formation of gametes as a result of meiosis, variants of loci with repetitive elements that do not code for the required proteins may occur. As a result, an individual with certain genetic rearrangements in this region may have an increased risk of developing a congenital disorder, particularly in cases where the non-functional allele is inherited dominantly. At the same time, there is still no routine or generally recognized diagnostic method to determine the sequence of the repetitive fragments. The functionally important RCCX locus consists of such repetitive fragments. The available knowledge about the genomic variants of the RCCX locus is fragmented, as there is no standardized method to determine its structure. It should be noted that in some structural variants of the RCCX locus, the sequence of protein-coding genes is disrupted, leading to the development of diseases such as congenital adrenal hyperplasia (CAH). Although genetic testing is generally accepted as a gold standard for CAH diagnosis, there are a myriad of strategies on which exact methods to use and in which order. The reason for this inconsistency lies in the complexity of the RCCX locus and the fact that each patient or carrier may have a highly individualized mutation or combination thereof. In this review, we have discussed all known methods that can be used to study the structure of the RCCX locus. As a result, optimal approaches are proposed for the diagnosis of the most common disease caused by lesions in the RCCX-CAH due to deficiency.
基因组中几乎相同的重复元件导致遗传遗传模式的可变性，特别是在 RCCX 基因座等区域，这种重复会导致结构变异。此外，在减数分裂形成配子的过程中，带有重复元件的基因座的变体可能会发生，而这些重复元件不编码所需的蛋白质。因此，该区域具有某些遗传重排的个体可能会增加患上先天性疾病的风险，特别是在非功能性等位基因显性遗传的情况下。同时，仍然没有常规或普遍认可的诊断方法来确定重复片段的序列。具有功能重要性的 RCCX 基因座由这样的重复片段组成。关于 RCCX 基因座的基因组变异的现有知识是零散的，因为没有标准化的方法来确定其结构。值得注意的是，在 RCCX 基因座的某些结构变体中，编码蛋白质的基因序列被破坏，导致先天性肾上腺增生症 (CAH) 等疾病的发展。虽然遗传测试通常被认为是 CAH 诊断的金标准，但有许多策略可以用来确定使用的确切方法和顺序。这种不一致的原因在于 RCCX 基因座的复杂性，以及每个患者或携带者可能具有高度个体化的突变或其组合的事实。在这篇综述中，我们讨论了可以用于研究 RCCX 基因座结构的所有已知方法。因此，提出了针对由于 缺乏导致的 RCCX-CAH 病变引起的最常见疾病的诊断的最佳方法。
