Center of Genetic and Prenatal Diagnosis, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Medical Records, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Endocr Pract. 2021 Feb;27(2):137-145. doi: 10.4158/EP-2020-0478. Epub 2020 Dec 8.
17 α-hydroxylase/17, 20-lyase deficiency (17-OHD) is a rare recessive hereditary disease that can be attributed to cytochrome P450 17 α-hydroxylase deficiency caused by CYP17A1 gene mutations.
A large cohort of 10 Chinese Han patients with 17-OHD from 2012 to 2020 were enrolled. The clinical and biochemical features were investigated, and genetic mutations of CYP17A1 were analyzed by polymerase chain reaction-Sanger sequencing. Karyotype identification and the SRY gene test were also carried out. In silico analysis was used to predict the effects of genetic mutations on the protein function.
All patients were female. Common complaints were hypertension, hypokalemia, and primary amenorrhea. The karyotype was 46, XY, and the SRY gene was detected in 7 patients; the karyotype was XX in the remaining 3 patients. A total of 7 mutations including Y329N, Y329X, Y329Lfs∗, R96W, A82D, S380N, and A487_P489del have been identified in the CYP17A1 gene. The Y329Lfs∗ mutation was found in 9/10 (90%) of patients with a high allele frequency of 70%. In silico prediction showed that a novel variant of c.1139G>A (S380N) occurs at a conserved residue and can cause disease.
We presented a detailed description of the clinical and genetic characteristics in Chinese patients with 17-OHD and concluded that Y329Lfs∗ mutation of CYP17A1 is prevalent in the Chinese Han population. Therefore, hotspot screening by polymerase chain reaction-Sanger sequencing for exon 6 of CYP17A1 could contribute to the rapid diagnosis of 17-OHD in China. Genetic counseling based on the genetic diagnosis for at-risk relatives is advised.
17α-羟化酶/17,20-裂合酶缺乏症（17-OHD）是一种罕见的隐性遗传性疾病，可归因于 CYP17A1 基因突变导致的细胞色素 P450 17α-羟化酶缺乏。
纳入了 2012 年至 2020 年期间的 10 例中国汉族 17-OHD 患者的大型队列。对临床和生化特征进行了研究，并通过聚合酶链反应-桑格测序分析了 CYP17A1 的基因突变。还进行了核型鉴定和 SRY 基因检测。采用计算机模拟分析预测基因突变对蛋白质功能的影响。
所有患者均为女性。常见的主诉为高血压、低血钾和原发性闭经。核型为 46，XY，7 例患者检测到 SRY 基因；其余 3 例患者核型为 XX。在 CYP17A1 基因中总共发现了 7 种突变，包括 Y329N、Y329X、Y329Lfs∗、R96W、A82D、S380N 和 A487_P489del。Y329Lfs∗突变在 10 例患者中的 9 例（90%）中发现，等位基因频率高达 70%。计算机模拟预测表明，c.1139G>A（S380N）的新型变体发生在保守残基处，可导致疾病。
我们详细描述了中国 17-OHD 患者的临床和遗传特征，并得出结论，CYP17A1 的 Y329Lfs∗突变在中国汉族人群中较为普遍。因此，通过聚合酶链反应-桑格测序对 CYP17A1 的外显子 6 进行热点筛查有助于快速诊断中国的 17-OHD。建议对高危亲属进行基于遗传诊断的遗传咨询。
