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Endocrinol Metab : Endocrinology and Metabolism


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Su Yeon Kim  (Kim SY) 1 Article
Endocrine Research
Functional Identification of Compound Heterozygous Mutations in the CYP17A1 Gene Resulting in Combined 17α-Hydroxylase/17,20-Lyase Deficiency
Eun Yeong Mo, Ji-young Lee, Su Yeon Kim, Min Ji Kim, Eun Sook Kim, Seungok Lee, Je Ho Han, Sung-dae Moon
Endocrinol Metab. 2018;33(3):413-422.   Published online September 18, 2018
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AbstractAbstract PDFPubReader   ePub   

We previously reported a patient with congenital adrenal hyperplasia (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (CYP17A1) gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation. The aim of this study was to investigate the functional properties of a new allele present in a compound heterozygote of CYP17A1.


To understand how p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and mutant CYP17A1 cDNAs were cloned into flag-tagged pcDNA3 vector and introduced into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels of CYP17A1 were then analyzed. And the activities of 17α-hydroxylase and 17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone to 17α-hydroxyprogesterone and of 17α-hydroxypregnenolone to dehydroepiandrosterone, respectively. In addition a computer model was used to create the three-dimensional structure of the mutant CYP17A1 enzymes.


Production of the p.His373Leu mutant protein was significantly lower than that of the wild type protein, and the p.Glu383fsX36 protein was hardly produced. Similarly the enzymatic activity derived from the p.His373Leu mutant vector was significantly lower than that obtained from the wild type vector, and little activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling of the enzyme showed that p.His373 was located in region important for heme-binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant protein formed a heme-binding structure.


Enzyme activity measured in both mutants disappeared completely in both 17α-hydroxylase and 17,20-lyase. This result accounts for the clinical manifestations of the patient with the compound heterozygous CYP17A1 mutations.


Citations to this article as recorded by  
  • A rare case of 17α-hydroxylase/17, 20-lyase deficiency: Clinical and genetic findings and follow-up outcomes
    Li-Zhen Dai, Hong Ma, Jian-Fang Ke, Chen-Shi Lin, Yanling Huang, Yuan Tian, Danling Chen
    Women's Health.2022; 18: 174550572211225.     CrossRef
  • Novel mutations of the CYP17A1 gene in four Chinese 46,XX cases with partial 17a-hydroxylase/17,20-lyase deficiency
    Yanjie Xia, Panlai Shi, Junke Xia, Huijuan Zhang, Lijun Xu, Xiangdong Kong
    Steroids.2021; 173: 108873.     CrossRef
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