A unique exonic splicing mutation in the CYP17A1 gene as the cause for steroid 17{alpha}-hydroxylase deficiency.


BACKGROUND:17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by a mutation in the CYP17A1 gene is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. The majority of CYP17A1 mutations are located in the coding sequence, and several intronic splicing site mutations have been reported. OBJECTIVE:A 2.5-year-old girl with 46,XY disordered sex development exhibited a nearly normal basal cortisol level and reduced sexual steroids. This study is aimed to explore the molecular basis and analyze its possible influence on the phenotype of the patient. METHODS AND RESULTS:Mutation analysis revealed compound heterozygous CYP17A1 mutations, with c.985_987delinsAA in one allele and a synonymous substitution (c.1263G>A) in another allele. In vitro expression analysis of the allelic minigene showed that the novel nucleotide variation located in exon 8 induces a splicing signal, which results in an aberrant splicing of CYP17A1 mRNA and a missing portion of exon 8. The translation product includes the deletion of six or seven amino acids from residue position 415 without causing a frameshift. Consistent with the result of molecular modeling, functional studies in transiently transfected HEK-293T cells with the aberrantly spliced enzyme proteins showed that the deleted proteins completely abolished the enzyme activity. However, RT-PCR indicated the existence of a small fraction of normal, functionally intact enzyme, which may explain the partial masculinization of this patient. CONCLUSION:This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17OHD phenotype. It also demonstrates the importance of studying synonymous change in such patients with less severe phenotype.


Eur J Endocrinol


Qiao J,Han B,Liu BL,Liu W,Wu JJ,Pan CM,Jiang H,Gu T,Jiang BR,Zhu H,Lu YL,Wu WL,Chen MD,Song HD




Has Abstract


2011-04-01 00:00:00














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    abstract:OBJECTIVE:To correlate anthropometric, computed tomography and fat cell data from abdominal regions with the levels of serum insulin, C-peptide, leptin, tumor necrosis factor-alpha (TNF-alpha), testosterone, 17beta-estradiol, androstenedione, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SH...

    journal_title:European journal of endocrinology

    pub_type: 临床试验,杂志文章


    authors: Garaulet M,Pérex-Llamas F,Fuente T,Zamora S,Tebar FJ

    更新日期:2000-11-01 00:00:00

  • Immunohistochemical detection of GHRH and its receptor splice variant 1 in primary human breast cancers.

    abstract:OBJECTIVE:GHRH is secreted by the hypothalamus and, upon binding to specific GHRH receptors in the pituitary, stimulates growth hormone (GH) production and release from the pituitary. In addition to this neuroendocrine action, accumulated evidence implies additional roles for GHRH in carcinogenesis in non-pituitary tis...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Chatzistamou I,Schally AV,Kiaris H,Politi E,Varga J,Kanellis G,Kalofoutis A,Pafiti A,Koutselini H

    更新日期:2004-09-01 00:00:00

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    journal_title:European journal of endocrinology

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    authors: Mouritsen A,Aksglaede L,Soerensen K,Hagen CP,Petersen JH,Main KM,Juul A

    更新日期:2012-12-31 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 临床试验,杂志文章


    authors: McKnight JA,McCance DR,Sheridan B,Atkinson AB

    更新日期:1995-04-01 00:00:00

  • Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism.

    abstract:BACKGROUND:Hyperthyroidism is a risk factor for reduced bone mineral density (BMD) and osteoporotic fractures. Vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) is a radiological method of visualization of the spine, which enables patient comfort and reduced radiation exposure. OBJECTIVES:T...

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    pub_type: 杂志文章


    authors: Barbosa AP,Rui Mascarenhas M,Silva CF,Távora I,Bicho M,do Carmo I,de Oliveira AG

    更新日期:2015-02-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章,多中心研究


    authors: Pepe G,Corica D,De Sanctis L,Salerno M,Faienza MF,Tessaris D,Tuli G,Scala I,Penta L,Alibrandi A,Pajno GB,Aversa T,Wasniewska M,Thyroid Study Group of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED).

    更新日期:2020-04-01 00:00:00

  • Differential subcellular distribution of rat prostatic steroid 5alpha-reductase isozyme activities.

    abstract::The rat prostate, a classical androgen-target tissue, contains both known isozymes of steroid 5alpha-reductase. i.e. type I and type II. So far, the role of the type I isozyme has been proposed as catabolic. The abundant expression of type I 5alpha-reductase in an androgen-target tissue is therefore puzzling. Assessme...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Span PN,Sweep CG,Benraad TJ,Smals A

    更新日期:1996-03-01 00:00:00

  • Preoperative diagnosis of insulinoma: low body mass index, young age, and female gender are associated with negative imaging by endoscopic ultrasound.

    abstract:OBJECTIVE:Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10-20% of insulinom...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Kann PH,Ivan D,Pfützner A,Forst T,Langer P,Schaefer S

    更新日期:2007-08-01 00:00:00

  • Impact of subclinical hypothyroidism on the coronary artery disease in apparently healthy subjects.

    abstract:OBJECTIVE:Cardiovascular disease (CVD) occurs frequently and may progress more rapidly in overt hypothyroidism (OVH). However, the role of mild thyroid failure as a risk factor for CVD is not clear. This study is aimed at exploring the association between subclinical hypothyroidism (SCH) and coronary artery disease (CA...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Park YJ,Lee YJ,Choi SI,Chun EJ,Jang HC,Chang HJ

    更新日期:2011-07-01 00:00:00

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    abstract::In recent years, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has emerged as an important tool for the postoperative management of patients with differentiated thyroid cancer (DTC) and it is widely used in selected clinical situations. The most valuable role that FDG...

    journal_title:European journal of endocrinology

    pub_type: 杂志文章,评审


    authors: Salvatori M,Biondi B,Rufini V

    更新日期:2015-09-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章,随机对照试验


    authors: Frost RJ,Sonne C,Wehr U,Stempfle HU

    更新日期:2007-03-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章,多中心研究


    authors: Lake JE,Debroy P,Ng D,Erlandson KM,Kingsley LA,Palella FJ,Budoff MJ,Post WS,Brown TT

    更新日期:2019-10-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Iranmanesh A,South S,Liem AY,Clemmons D,Thorner MO,Weltman A,Veldhuis JD

    更新日期:1998-07-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Parikka V,Peng Z,Hentunen T,Risteli J,Elo T,Väänänen HK,Härkönen P

    更新日期:2005-02-01 00:00:00

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    abstract::Puberty is the period during which we attain adult secondary sexual characteristics and reproductive capability. Its onset depends upon reactivation of pulsative GNRH, secretion from its relative quiescence during childhood, on the background of intact potential for pituitary-gonadal function. This review is intended:...

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    pub_type: 杂志文章,评审


    authors: Dunkel L,Quinton R

    更新日期:2014-06-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Ferrari E,Cravello L,Muzzoni B,Casarotti D,Paltro M,Solerte SB,Fioravanti M,Cuzzoni G,Pontiggia B,Magri F

    更新日期:2001-04-01 00:00:00

  • Use of radiotherapy after pituitary surgery for non-functioning pituitary adenomas.

    abstract::Surgery is the treatment of choice for non-functioning pituitary macroadenomas (NFPAs). In cases of postoperative remnant growth or tumor recurrence, radiotherapy (RT) can be considered. The role of RT in the postoperative management of NFPAs is still debated. The main arguments against routine use of RT are the lack ...

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    pub_type: 杂志文章,评审


    authors: Chanson P,Dormoy A,Dekkers OM

    更新日期:2019-07-01 00:00:00

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    abstract:BACKGROUND/AIM:Our previous studies showed that administration of dexamethasone plus food increased serum leptin levels 100% more than dexamethasone alone. We hypothesized that this increase in leptin from the meal could result directly from the provision of fuel metabolites rather than from the meal-induced rise in in...

    journal_title:European journal of endocrinology

    pub_type: 临床试验,杂志文章


    authors: Garcia-Lorda P,Nash W,Roche A,Pi-Sunyer FX,Laferrere B

    更新日期:2003-06-01 00:00:00

  • The GH/IGF-I axis and longevity.

    abstract::Several converging lines of evidence obtained over the last years in a wide variety of experimental model organisms suggest that the ageing process is regulated by genes that encode proteins from the somatotroph axis: longevity genes like daf-2, which were identified using mutant Caenorhabditis elegans strains, turned...

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    更新日期:2004-08-01 00:00:00

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    更新日期:2018-02-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章,随机对照试验


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    pub_type: 杂志文章


    authors: Benhadi N,Wiersinga WM,Reitsma JB,Vrijkotte TG,Bonsel GJ

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    pub_type: 杂志文章


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    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Beck-Nielsen SS,Brock-Jacobsen B,Gram J,Brixen K,Jensen TK

    更新日期:2009-03-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Wu D,Li L,Yang M,Liu H,Yang G

    更新日期:2011-10-01 00:00:00

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    pub_type: 杂志文章


    authors: Hew-Butler T,Noakes TD,Soldin SJ,Verbalis JG

    更新日期:2008-12-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 临床试验,杂志文章


    authors: Tönshoff B,Blum WF,Vickers M,Kurilenko S,Mehls O,Ritz E

    更新日期:1995-04-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章


    authors: Thøgersen VB,Heickendorff L,Ledet T

    更新日期:1996-03-01 00:00:00

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    journal_title:European journal of endocrinology

    pub_type: 杂志文章,评审


    authors: Beck-Peccoz P,Persani L

    更新日期:1994-10-01 00:00:00