Clinical and genetic analyses of a Chinese female with 17α-hydroxylase/17,20-lyase deficiency

Abstract

Aims: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal recessive disease caused by CYP17 gene mutations. This disease is clinically characterised by hypertension, hypokalaemia, sexual infantilism in females or pseudohermaphroditism in males, and adrenal hyperplasia. This study aims to investigate a rare case of 17OHD accompanied by both cystic ovaries and massive adrenal mass.

Methods: This study performed clinical, hormonal, radiological and genetic analyses. Blood samples were collected from the patient for the genetic test. Genomic DNA was extracted from peripheral blood leukocytes, and the coding sequence abnormalities of CYP17 were assessed using polymerase chain reaction and direct sequencing analysis.

Results: The genetic analysis of CYP17 revealed compound heterozygous mutations in the individual. One was a mis-sense mutation of c.1226 C > G, which changes codon 409 in exon 7 from proline (CCG) to arginine (CGG). Another was a mutation of p.Val311Asp,fs,330X, which was first reported in a compound heterozygote mutation of Y329fs and V311fs from a Chinese patient.

Conclusion: This study presented a rare case of 17OHD accompanied by both cystic ovaries and massive adrenal mass. This study obtained significant information on the genotype–phenotype correlation of 17OHD.

Chinese abstract

目的：17α羟化酶/17,20裂解酶缺乏症（17OHD）是一种罕见的由CYP17基因突变导致的常染色隐形遗传病。该疾病临床表现为高血压、低血钾、女性生殖系统发育停顿或男性假两性畸形、肾上腺增生等。本研究目的在于报道一例罕见的17OHD伴囊性卵巢与巨大肾上腺肿块的病例。

方法：本研究进行了临床、激素、放射与基因分析。采集患者的血液样本进行基因测定。基因组DNA提取自外周血白细胞，CYP17编码序列的异常通过聚合酶链反应与直接测序分析进行测定。

结果：CYP17的基因分析表明该患者存在复合杂合突变。其一，是c.1226 C > G的误义突变，使外显子7中的密码子409由脯氨酸（CCG）变成了精氨酸（CGG）。其二，是p.Val311Asp,fs,330X的突变，首次报道出现在中国一例Y329fs与V311fs复合杂合突变的患者。

结论：本研究呈现了一例罕见的17OHD合并囊性卵巢与巨大肾上腺肿块的病例。研究获得了重要的17OHD基因型-表型间相互关系的信息。

• 17α-Hydroxylase/17,20-lyase deficiency
• adrenal mass
• CYP17 gene
• ovarian cysts

Acknowledgements

We thank the patient and collaborating physicians for their participation in this study.