Elsevier

Clinica Chimica Acta

Volume 412, Issues 13–14, 11 June 2011, Pages 1240-1243
Clinica Chimica Acta

Prevalence of common mutations in the CYP17A1 gene in Chinese Han population

https://doi.org/10.1016/j.cca.2011.03.019Get rights and content

Abstract

Background

Congenital adrenal hyperplasia owing to 17α-hydroxylase/17, 20-lyase deficiency is caused by genetic mutations in the CYP17A1 gene. To date, more than 80 different genetic lesions have been described in patients suffering from this disorder. We aimed to estimate the prevalence of CYP17A1 common mutations in Chinese Han population.

Methods

We first reported two female patients with 17α-hydroxylase deficiency based on their clinical features and molecular genetics, and then summarized all the mutations of CYP17A1 gene reported around the world. The most common mutations of CYP17A1 among Chinese Han were genotyped in additional 3245 healthy Chinese using Taqman-assays.

Results

The mutation spectrum in Asian is different from European decent. All healthy controls could detect two CYP17A1 mutations, D487-S488-F489 deletion and TAC329AA, with a prevalence of 1 in 1000 or 2 in 1000, respectively.

Conclusion

Our data demonstrates that these two mutations are major causes of 17α-hydroxylase deficiency in Chinese Han population.

Introduction

The 17α-hydroxylase deficiency (17OHD) is a rare autosomal recessive disorder with an estimated incidence of approximately 1 in 50,000 individuals which is the third after those of 21α-hydroxylase and 11β-hydroxylase deficiency in studies. It was initially described in 1966 by Biglieri et al. in a genotypical female [1] while New reported the first male patient in 1970 [2]. This disease affects both adrenal and gonadal glands which leads to hypertension, hypokalemia, male pseudohermaphroditism or female sexual infantilism, lower plasma cortisol with elevated ACTH, and suppression of renin–angiotensin system and aldosterone production. The disease is caused by mutations in the gene CYP17A1, which is located on chromosome 10q24.3 [3], [4] and consists of eight exons that spans 7003 bases and encodes 508 amino acids [5].

Up to now, more than 80 different mutations of human CYP17A1, genes have been reported around the world, including missense, splicing defect, duplication, insertion, and deletion mutations. These mutations have been known to cause either completely or partially, combined or isolated 17α-hydroxylase/17, 20-lyase enzyme deficiencies, although they are more prevalent in certain ethnic groups, particularly in Brazilians and Japanese.[5], [6] In this study, we report two Han Chinese families with 17α-hydroxylase/17, 20-lyase deficiency carrying heterozygous mutations in the CYP17A1 gene and try to identify the most common mutations of CYP17A1 among Chinese Han population.

Section snippets

Case report

Patient 1 in the first family, 21 years old, phenotypic female sought medical treatment because of primary amenorrhea, severe hypokalemia (2.3 mmol/L) and hypertension (150–170/100–120 mm Hg). Her karyotype was 46, XX. Medical examinations showed sexual infantilism including lack of axillary and pubic hair and breasts development (Tanner stage I). She had prepuberal female external genitalia and no uterus (This was also proved by the ultrasonography). Computed tomography revealed the presence of

Results and discussion

To understand the molecular basis of 17OHD disease, we performed a genetic analysis of two patients and their family members. PCR-direct sequencing revealed two kinds of mutations, of which were: (1) 6436–6438(TAC- > AA), causing amino acid Y329K, 418X (exon 6); (2) 1519–1527 (GACTCTTTC deletion), causing amino acid D487-S488-F489 deletion (exon 8)(Fig. 1). And the mutation of H373L, one of Asian common mutations in accordance with the reports ever before, is also reported in Han Chinese

Sources of funding

This work was supported by grants from National “863” project (No. 2006AA02A406) and “973” project (No. 2007CB512004).

Acknowledgment

We would like to thank Drs. Jinxiao Chu for her efforts in recruiting patients for this study.

References (23)

  • R.S. Sparkes et al.

    Regional mapping of genes encoding human steroidogenic enzymes: P450scc to 15q23–q24, adrenodoxin to 11q22; adrenodoxin reductase to 17q24–q25; and P450c17 to 10q24–q25

    DNA Cell Biol

    (1991)
  • Cited by (24)

    • Clinical and Genetic Characteristics of 17 α-Hydroxylase/17, 20-Lyase Deficiency: c.985_987delTACinsAA Mutation of CYP17A1 Prevalent in the Chinese Han Population

      2021, Endocrine Practice
      Citation Excerpt :

      It's clear that the genotype distributions of CYP17A1 highlight significant regional characteristics. Y329Lfs and c.1459_1467del have been reported to be common in the Han Chinese.14,19–23 Y329Lfs has been reported in 4 of 5 Chinese Han patients with 17-OHD from Henan Province.24

    • A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency, a case series of such mutations among Koreans and functional characteristics of a novel mutation

      2014, Metabolism: Clinical and Experimental
      Citation Excerpt :

      With this notion in mind, D487_F489 deletion has been described as the most common mutation of the CYP17A1 gene, especially in China [31–35,37,38]. Since D487_F489 deletion was first identified in a Thai patient [39], it has been frequently identified in China [31–35,37,38]. Haplotype analysis revealed that the D487_F489del of CYP17A1 came from common ancestors with identical shared haplotypes, suggesting the founder effect in the Asian population [35].

    • Identifying a novel mutation of CYP17A1 gene from five Chinese 17α-hydroxylase/17, 20-lyase deficiency patients

      2013, Gene
      Citation Excerpt :

      Previous research suggests that 17αhydroxylase/17,20-lyase deficiency (17OHD) may be the secondary cause of congenital adrenal hyperplasia (CAH) in Brazil, which is caused by CYP17A1 gene mutation and is characterized by hypertension, hypokalemia, the absence of pubertal development and hypergonadotropic hypogonadism in both sexes (Wei et al., 2006). Biglieri first reported this disease in 1966 (Biglieri et al., 1966), and since then, more than 80 inactivating mutations of P450c17 that lead to 17OHD have been reported (Bao et al., 2011). These mutations cause complete or partial, combined or isolated 17α-hydroxylase/17,20-lyase enzyme deficiencies.

    View all citing articles on Scopus
    1

    Xunna Bao and Hu Ding contributed equally to this work.

    View full text