A new compound heterozygous mutation in a female with 17α-hydroxylase/17,20-lyase deficiency, slipped capital femoral epiphysis, and adrenal myelolipoma

Abstract

17α-Hydroxylase/17,20-lyase deficiency (17-OHD) is a rare disease caused by mutations of the CYP17A1 gene. Slipped capital femoral epiphysis (SCFE) rarely occurs in adults. There are occasional reports of adrenal myelolipoma (AML) in 17-OHD. A 27-year-old Chinese female (46, XX) visited the hospital for SCFE and presented with continuous hypokalemia, absent spontaneous puberty, and hypertension. Hypergonadotropic hypogonadism was detected. The laboratory tests were consistent with 17-OHD. AML was considered based on the imaging examinations. A mutation analysis of the CYP17A1 gene identified the following compound heterozygous mutation: a frame-shift mutation, i.e. c.985_987delTACinsAA (p.Tyr329fs), that had been reported to be a common mutation in the Chinese population was found in exon 6. Another new nonsense mutation, i.e. c.1270C > T (p.Gln424*), that causes a premature termination codon was found in exon 8. Treatment with prednisone had poor efficacy. The administration of 0.75 mg dexamethasone and estradiol/dydrogesterone cyclic treatment significantly improved the patient’s symptoms. For the first time, we report a 17-OHD case accompanied by SCFE, AML, and a novel mutation site in the CYP17A1 gene. We provide insight into the clinical manifestations, genetic analysis, and treatment options of 17-OHD.

摘要

17α-羟化酶/ 17,20-裂解酶缺乏症（17-OHD）是由CYP17A1基因突变引起的一种罕见疾病。股骨骺滑脱（SCFE）也很少发生在成人身上。偶尔有17-OHD的肾上腺髓质脂肪瘤（AML）的报道。一名27岁的中国女性（46岁, XX岁）到SCFE医院就诊, 出现持续性低钾血症, 无自发性青春期和高血压。检查有高促性腺激素性性腺功能减退症。实验室检查与17-OHD一致。通过影像学检查诊断AML。CYP17A1基因突变分析鉴定出以下复合杂合突变：在外显子6中发现了一个移码突变, 即c985_987delTACinsAA（p.Tyr329fs）, 据报道它是中国人群中常见的突变。另一个为在外显子8中发现引起过早终止密码子出现的一种新的无义突变, 即c1270C> T（p.Gln424）。用泼尼松治疗效果差。给予0.75mg地塞米松和雌二醇/地屈孕酮周期治疗显著改善了患者的症状。我们第一次报道了关于17-OHD伴有SCFE, AML和CYP17A1基因突变新位点的病例。我们也提供17-OHD的临床表现, 遗传分析和治疗选择的见解。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• Congenital adrenal hyperplasia
• 17α-hydroxylase/17
• 20-lyase deficiency
• CYP17A1
• slipped capital femoral epiphysis
• adrenal myelolipoma

Acknowledgements

We deeply thank Professor Hongwei Liang (Department of CT room, the Second Affiliated Hospital of Harbin Medical University, Harbin, China) for his help and support with the imaging diagnosis of the adrenal.

Disclosure statement

The authors declare that they have no conflicts of interest concerning this work.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China (81770809) and the Graduate Innovation Fund of Harbin Medical University (YJSCX2017-59HYD).