Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
Mol Cell Endocrinol. 2020 Nov 1;517:110968. doi: 10.1016/j.mce.2020.110968. Epub 2020 Aug 4.
Congenital hypogonadotropic hypogonadism (CHH) is caused by dysfunction of hypothalamic gonadotropic-releasing hormone (GnRH) axis. The condition is both clinically and genetically heterogeneous with more than 40 genes implicated in pathogenesis. The goal of the present study was to identify causative mutations in CHH individuals employing 2 step procedure with a targeted NGS panel as first-line diagnostics and subsequently whole exome sequencing in unsolved cases. Known or novel potentially deleterious variants were found in 28 out of 47 tested CHH patients. Molecular diagnosis was reached in 19/47 CHH cases. In 13 cases monogenic variants were identified in ANOS1, FGFR1, GNRHR, CHD7, SOX10, and PROKR2, while 6 patients showed digenic or trigenic inheritance patterns. The achieved diagnostic rate was comparable to other studies on genetics of CHH. By evaluating and reporting more patients with CHH we make progress in unravelling its genetic complexity and move a step closer to personalised medicine.
先天性低促性腺激素性性腺功能减退症（CHH）是由下丘脑促性腺激素释放激素（GnRH）轴功能障碍引起的。该疾病在临床上和遗传上均具有异质性，超过 40 种基因与发病机制有关。本研究的目的是通过两步法，即首先使用靶向 NGS 面板进行一线诊断，然后在未解决的病例中进行全外显子组测序，来鉴定 CHH 个体中的致病突变。在 47 名接受测试的 CHH 患者中，有 28 名发现了已知或新的潜在有害变异。在 47 例 CHH 中，有 19 例分子诊断明确。在 13 例中，鉴定出 ANOS1、FGFR1、GNRHR、CHD7、SOX10 和 PROKR2 中的单基因变异，而 6 例患者表现出双基因或三基因遗传模式。所达到的诊断率与其他关于 CHH 遗传学的研究相当。通过评估和报告更多的 CHH 患者，我们在揭示其遗传复杂性方面取得了进展，并朝着个体化医疗迈进了一步。
