Presentation, Diagnosis, and Follow-Up Characteristics of 17α-Hydroxylase Deficiency Cases with Exon 1-6 Deletion (Founder Mutation) in the CYP17A1Gene: 20-Year Single-Center Experience.

IF 2.4 4区 医学 Q2 DEVELOPMENTAL BIOLOGY
Ismail Dundar, Aysehan Akinci, Emine Camtosun, Nurdan Ciftci, Leman Kayas
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引用次数: 0

Abstract

Context: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol synthesis, as well as an increased mineralocorticoid effect.

Aim: This study aimed to evaluate the clinical, biochemical, and molecular characteristics of patients with 17OHD and to discuss the diagnosis, treatment, and follow-up process.

Methods: Age, symptoms, anthropometric measurements, blood pressure, and hormonal, biochemical, and chromosomal analysis results of 13 patients diagnosed with 17OHD between 2003 and 2022 were recorded at admission and during follow-up. Whole gene next-generation sequencing was performed for the CYP17A1 gene. Multiplex ligation-dependent probe amplification was used to detect deletions in patients without point mutations in CYP17A1.

Results: The median age at diagnosis was 14.0 (3.5-16.8) years. Nine of 13 patients (69.2%) had 46,XY karyotypes. All patients were phenotypically female and were raised as girls. The most common reasons for admission were the absence of puberty and amenorrhea (n = 8, 61.5%), followed by hypertension (n = 3, 23.0%), and family screening (n = 2, 15.3%). At the time of diagnosis, hypertension was detected in 10 (76.9%) patients, and 11 (84.6%) patients had hypokalemia.

Conclusions: 17OHD should be considered in patients with pubertal delay/primary amenorrhea, hypertension, and hypokalemia. Adrenal function should be included in the clinical study of hypergonadotropic hypogonadism, after excluding Turner syndrome, in all 46,XX females. Deletion in the CYP17A1 gene, including exons 1-6, is the founder mutation for Turkey's east and southeast regions.

cyp17a1基因外显子1-6缺失(方正突变)的17α-羟化酶缺乏症的表现、诊断和随访特征:20年单中心经验
背景:17α-羟化酶/17,20裂解酶缺乏症(17OHD)的特征是性类固醇和皮质醇合成减少,以及矿化皮质激素作用增加。目的:评价17OHD患者的临床、生化及分子特征,探讨其诊断、治疗及随访过程。方法:记录2003 ~ 2022年间13例17OHD患者入院时及随访时的年龄、症状、人体测量、血压、激素、生化及染色体分析结果。对CYP17A1基因进行全基因下一代测序。多重连接依赖探针扩增用于检测没有CYP17A1点突变的患者的缺失。结果:中位诊断年龄为14.0(3.5 ~ 16.8)岁。13例患者中有9例(69.2%)为46xy核型。所有患者均为女性,被当作女孩抚养。最常见的入院原因是没有青春期和闭经(n = 8, 61.5%),其次是高血压(n = 3, 23.0%)和家庭筛查(n = 2, 15.3%)。诊断时高血压10例(76.9%),低血钾11例(84.6%)。结论:青春期延迟/原发性闭经、高血压、低钾血症患者应考虑17OHD。肾上腺功能应纳入促性腺功能亢进症的临床研究,在排除特纳综合征后,所有46,xx名女性。CYP17A1基因(包括外显子1-6)的缺失是土耳其东部和东南部地区的创始突变。
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来源期刊
Sexual Development
Sexual Development 生物-发育生物学
CiteScore
4.00
自引率
4.30%
发文量
25
审稿时长
>12 weeks
期刊介绍: Recent discoveries in experimental and clinical research have led to impressive advances in our knowledge of the genetic and environmental mechanisms governing sex determination and differentiation, their evolution as well as the mutations or endocrine and metabolic abnormalities that interfere with normal gonadal development. ‘Sexual Development’ provides a unique forum for this rapidly expanding field. Its broad scope covers all aspects of genetics, molecular biology, embryology, endocrinology, evolution and pathology of sex determination and differentiation in humans and animals. It publishes high-quality original research manuscripts, review articles, short reports, case reports and commentaries. An internationally renowned and multidisciplinary editorial team of three chief editors, ten prominent scientists serving as section editors, and a distinguished panel of editorial board members ensures fast and author-friendly editorial processing and peer reviewing.
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