17α-Hydroxylase/17,20-Lyase Deficiency Caused by a Novel Homozygous Mutation (Y27Stop) in the Cytochrome CYP17 Gene

Müssig, Karsten; Kaltenbach, Simone; Machicao, Fausto; Maser-Gluth, Christiane; Hartmann, Michaela F.; Wudy, Stefan A.; Schnauder, Günter; Häring, Hans‐Ulrich; Seif, F. J.; Gallwitz, Baptist

doi:10.1210/jc.2005-0136

Cited by 30 publications

(21 citation statements)

References 19 publications

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“…However, 10-15% of reported patients are normotensive at presentation [Kater and Biglieri, 1994]. Normal renin concentrations in hypertensive patients and low renin concentrations in normotensive patients have been described [Van Den Akker et al, 2002;Müssig et al, 2005]. This is similar to our findings with all patients having suppressed renin concentrations and only sibling 1 presenting with hypertension.…”

Section: Discussionsupporting

confidence: 90%

Identification of a Novel Large CYP17A1 Deletion by MLPA Analysis in a Family with Classic 17α-Hydroxylase Deficiency

Türkkahraman

Güran

Ivison

et al. 2015

Sex Dev

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Steroid 17α-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia caused by mutations in the 17α-hydroxylase (CYP17A1) gene. CYP17A1 is a key enzyme in the biosynthesis of adrenal and gonadal steroid hormones facilitating both 17α-hydroxylase and 17,20-lyase activities. We characterized a partial CYP17A1 deletion in a Kurdish family with 17OHD by multiplex ligation-dependent probe amplification (MLPA). The index patient presented with amenorrhea and lack of pubertal development. Investigations established the diagnosis of 46,XY disorder of sex development (DSD). She is the daughter of consanguineous parents and has 2 sisters with similar clinical presentation. All patients showed biochemical signs of primary adrenal and gonadal insufficiency. The molecular genetic analysis by PCR suggested a deletion spanning exons 1-6 of the CYP17A1 gene. MLPA analysis confirmed the large partial CYP17A1 deletion in patients and parents in homozygous and heterozygous state, respectively. This is the first report employing MLPA for mutation analysis to detect a deletion of CYP17A1 spanning multiple exons in 3 patients with classic 17OHD. Therefore, it is important to consider large partial CYP17A1 deletions in 17OHD in addition to point mutations in cases where no segregation analysis is possible to determine the correct genotype.

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Section: Discussionsupporting

confidence: 90%

Identification of a Novel Large CYP17A1 Deletion by MLPA Analysis in a Family with Classic 17α-Hydroxylase Deficiency

Türkkahraman

Güran

Ivison

et al. 2015

Sex Dev

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“…Furthermore, sparse pubic hair development occurred in some CYP17A1 deficiency patients with spontaneous puberty (4,(28)(29)(30)(31)(32), pubic as well as axillary hair growth is noted after cyclic estrogen/gestagen treatment similar to our case in only one Turkish patient with 17OHD, living in Germany (13). It might be a coincidence that both of the patients are of Turkish origin, however, genetic factors related to sexual hair growth might be considered in that aspect.…”

Section: Discussionsupporting

confidence: 78%

“…Similarly, most of the cases with 17OHD have variations in the blood pressure, serum potassium, and the aldosterone secretion rate even in the patients carrying same mutations (3,5). Furthermore, normal plasma renin levels in hypertensive patients and low renin levels in normotensive patients were also described (13,14). This heterogeneity has not been completely understood, but many factors, including the severity of CYP17A1 mutation, dietary sodium intake, environment, and other genetic factors regulating electrolyte metabolism might have a role in these mechanisms.…”

Section: Discussionmentioning

confidence: 91%

Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair

Turan¹,

Bereket²,

Güran³

et al. 2009

European Journal of Endocrinology

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Objective: 17-Hydroxylase/17,20-lyase deficiency (17OHD) results from mutations in the CYP17A1 gene, leading to failure to synthesize cortisol, adrenal androgens, and gonadal steroids. Adrenarche is a consequence of the increased production of adrenal androgens. Here, we report a case carrying novel R239Q mutation causing complete functional loss of CYP17A1, and thus absence of adrenal and gonadal sex hormone production. The patient has had unexpected pubic hair development and insufficient breast development with estrogen replacement therapy. Possible mechanisms leading to pubic hair development and breast underdevelopment are discussed. Patient and methods: A 15-year-old female born to consanguineous parents presented with the lack of full breast development and irregular menses after the age of 14 years. She had Tanner III breast development on one side, Tanner I on the other side and Tanner I pubic hair and, no axillary hair development. The serum levels of FSH, LH, and progesterone were high and, estradiol was low. The measurement of basal and ACTH-stimulated steroids was consistent with the diagnosis of 17OHD. Genetic analysis revealed novel homozygous mutation R239Q in CYP17A1 gene. Therapy with hydrocortisone was initiated and followed by the addition of conjugated estrogen. Her breast development did not improve considerably, however, pubic hair development started after estrogen treatment in spite of undetectable serum levels of androgens. Conclusion: This case study suggests that estrogen exerts a permissive effect on pubic hair development in girls, even in the presence of very low-circulating androgens, and impaired breast development might be due to estrogen/progesterone imbalance in breast tissue.

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“…The disease is caused by mutations in the CYP17A1 gene which encodes cytochrome P450c17, an enzyme expressed in the adrenal cortex and the gonads displaying both 17α-hydroxylase and 17,20-lyase activities, among others (4)(5)(6)(7)(8)(9)(10)(11)(12). The former activity is carried out by converting pregnenolone and progesterone to 17α-hydroxypregnenolone (17OHPreg) and 17α-hydroxyprogesterone (17OHP), respectively, whereas the latter performs the C17-20 side-chain cleavage of 17OHPreg to yield DHEA, an androgen precursor in the adrenal zona reticulata, ovaries and testes.…”

mentioning

confidence: 99%

Distinctive profile of the 17-hydroxylase and 17,20-lyase activities revealed by urinary steroid metabolomes of patients with CYP17 deficiency

Neres

Auchus

Shackleton

et al. 2010

Arq Bras Endocrinol Metab

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17α-Hydroxylase/17,20-Lyase Deficiency Caused by a Novel Homozygous Mutation (Y27Stop) in the Cytochrome CYP17 Gene

Cited by 30 publications

References 19 publications

Identification of a Novel Large <b><i>CYP17A1 </i></b>Deletion by MLPA Analysis in a Family with Classic 17α-Hydroxylase Deficiency

Identification of a Novel Large <b><i>CYP17A1 </i></b>Deletion by MLPA Analysis in a Family with Classic 17α-Hydroxylase Deficiency

Puberty in a case with novel 17-hydroxylase mutation and the putative role of estrogen in development of pubic hair

Distinctive profile of the 17-hydroxylase and 17,20-lyase activities revealed by urinary steroid metabolomes of patients with CYP17 deficiency

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