A rare cause of delayed puberty in two cases with 46,XX and 46,XY karyotype: 17 α-hydroxylase deficiency due to a novel variant in CYP17A1 gene

Abstract

Aims: 17α-hydroxylase deficiency is a rare form of congenital adrenal hyperplasia (CAH) which is inherited autosomal recessive. It occurs result of a mutations in gene cytochrome (CYP)17A1, which encodes both 17α-hydroxylase and 17,20-lyase enzymes. The main clinical findings of the disease are delayed puberty, primary amenorrhea in females, and disorders of sex development (DSD) in males. Also, hypertension and hypokalemia can be seen in both sexes. In this paper, we describe the clinical and genetic changes of two patients with 46,XY and 46,XX karyotypes from two different families who were diagnosed with complete 17α-hydroxylase enzyme deficiency.

Methods: In this study various methods including clinical, hormonal, radiological and genetic analyzes were used. Blood samples were obtained for genetic tests. Genomic DNA was extracted from peripheral blood leukocytes, and coding sequence abnormalities of the CYP17 gene were assessed by polymerase chain reaction and direct sequencing analysis.

Results: 17α-hydroxylase deficiency was diagnosed in 2 patients with 46,XX and 46,XY karyotype who presented with hypertension and delayed puberty. The pQ80 * (c.238C > T) mutation detected in both cases was evaluated as a novel variant.

摘要

目的：17α羟化酶缺乏症是一种罕见的先天性肾上腺皮质增生症（CAH）, 是一种常染色体隐性遗传病。是由细胞色素（CYP）17A1基因突变的结果, 该基因编码17个半羟化酶和17-、20-裂解酶。该病的主要临床表现为青春期延迟, 女性原发性闭经, 男性性发育障碍（DSD）。此外, 高血压和低钾血症在两种性别中都可见。本文, 我们报道了两个不同家族的46, XY和46, XX染色体核型的患者, 他们被诊断为完全17α羟化酶缺乏症。

方法：该研究采用了多种方法进行研究, 包括临床特点、激素、放射学和遗传学分析。采集血样进行基因检测。从外周血的白细胞中提取基因组DNA, 通过聚合酶链反应和直接测序分析评价CYP17基因编码序列的异常情况。

结果：2例核型分别为46, XX和46, XY的患者诊断为17α羟化酶缺乏, 均表现为高血压和青春期延迟。在这两例均检测到pQ80(c.238C>T）突变, 被认为是一个新的变异。

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:

• 17α-hydroxylase
• CYP17A1 gene
• delayed puberty
• hypertension
• primary amenorrhea

Disclosure statement

The authors report no conflict of interest.