A 5′-Splice Site Mutation in the Cytochrome P450 Steroid 17α-Hydroxylase Gene in 17α-Hydroxylase Deficiency

Yamaguchi, Hideki; Nakazato, Masamitsu; Miyazato, Minoru; Kangawa, Kenji; Matsukura, Shigeru

doi:10.1210/jcem.82.6.4027

Cited by 13 publications

(3 citation statements)

References 14 publications

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“…After this, approximately 150 cases of 17OHD have been reported, but the cases with 17OHD reported from Asian countries, such as China, Korea, and Japan, are limited (Fardella et al, 1993;Yamaguchi et al, 1997;Suzuki et al, 1998;Lam et al, 2001;Hahm et al, 2003;Qiao et al, 2003). In this study, we report a new compound heterozygous mutation in the CYP17A1 gene in a Chinese child with 17OHD.…”

Section: Introductionmentioning

confidence: 60%

New compound heterozygous mutations of p. Thr101Ilefs*2 and p. Thr306Ale in a child from a Chinese family with 17α-hydroxylase/17, 20-lyase deficiency

Xiao¹,

Zhang²,

T³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We determined whether a child with 17a-hydroxylase/17, 20-lyase deficiency possessed the sex-determining region (SRY) gene, and examined the mutations present in the CYP17A1 gene that led to 17a-hydroxylase/17, 20-lyase deficiency. In the child, karyotype analysis was performed and polymerase chain reaction analysis and electrophoretic techniques were used to identify the SRY gene. A total of 50 normal individuals were included as a control group. Polymerase chain reaction and DNA sequencing were used to identify CYP17A1 gene mutations in all samples. The karyotype of the child was 46, XY, which was inconsistent with her social sex, SRY was positive, and a compound heterozygous mutation p. Thr101Ilefs*2 in exon 2 and p. Thr306Ale in exon 5 were identified in the CYP17A1 gene. These mutations were inherited from her parents. In the 20 normal individuals, these mutations were not identified. In the child, sex reversal may have been caused by CYP17A1 mutations. The compound heterozygous

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Section: Introductionmentioning

confidence: 60%

New compound heterozygous mutations of p. Thr101Ilefs*2 and p. Thr306Ale in a child from a Chinese family with 17α-hydroxylase/17, 20-lyase deficiency

Xiao¹,

Zhang²,

T³

et al. 2015

Genet. Mol. Res.

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“…Although elevated ACTH induces excess levels of mineralocorticoid and then hypertension and hypokalemia, the plasma aldosterone concentration (PAC) in 17OHD patients is typi-cally low. However, some patients have an elevated PAC, however, making diagnosis difficult (4)(5)(6). The lack of 17,20-lyase activity disrupts adrenal androgen synthesis.…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of Plasma Immunoassayable Aldosterone in a Mild Form of 17 Alpha-Hydroxylase/17,20-lyase Deficiency Diagnosed at the Age of 50

Ueda

Usui

Watanabe

et al. 2015

AACE Clinical Case Reports

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Objective: 17 Alpha-hydroxylase/17,20-lyase deficiency (17OHD) is a form of congenital adrenal hyperplasia caused by homozygous or compound heterozygous mutations in the CYP17A1 gene. Impaired activities of 17 alphahydroxylase and 17,20-lyase typically induce hypertension, hypokalemia, and amenorrhea, with the vast majority of patients with 17OHD are diagnosed in adolescence.Methods: We present a case of 17OHD diagnosed at the age of 50 with complete endocrinologic investigations and genetic analysis.Results: The patient had hypokalemia and a low cortisol level. Her dehydroepiandrosterone sulfate (DHEA-S) and androstenedione levels were undetectable, although her adrenocorticotropic hormone (ACTH) level was elevated. She had markedly elevated pregnenolone, progesterone, deoxycorticosterone, and corticosterone levels. In addition, her plasma renin activity and plasma aldosterone concentration were suppressed and elevated, respectively.Rapid ACTH stimulation increased the hormones upstream of 17 alpha-hydroxylase, and overnight 1-mg dexamethasone suppressed them. The patient was thus diagnosed with 17OHD. Genetic testing confirmed the diagnosis, revealing 2 distinct mutations in the CYP17A1 gene, c985_987delTACinsAA and R416C, which have been previously reported.Conclusion: The present case is a mild form of 17OHD that had gone undiagnosed until the age of 50. The R416C genotype seems to relate to a mild phenotype. Mild 17OHD may remain undiagnosed or be misdiagnosed as primary aldosteronism or idiopathic hyperaldosteronism.

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“…The gene for this enzyme (CYP17) is located on chromosome 10q24.3 [2], and mutations in the CYP17 gene have been reported to cause 17α-hydroxylase/17,20-lyase deficiency [3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. Adrenal 17α-hydroxylase deficiency is characterized by impaired production of cortisol and compensated hypersecretion of adrenocorticotropin, which stimulates the synthesis of large amounts of 11-deoxycorticosterone and corticosterone, leading to hypertension, hypokalemia, and a suppressed renin-angiotensin system.…”

Section: Introductionmentioning

confidence: 99%

New Compound Heterozygous Mutation in the <i>CYP17</i> Gene in a 46,XY Girl with 17α-Hydroxylase/17,20-Lyase Deficiency

Katsumata¹,

Satoh

Mikami

et al. 2001

Horm Res Paediatr

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Background: 17α-Hydroxylase/17,20-lyase deficiency is caused by a defect of P450c17 which catalyzes both 17α-hydroxylase and 17,20-lyase reactions in adrenal glands and gonads. Results: In the present study, we analyzed the CYP17 gene in a Japanese patient with 17α-hydroxylase/17,20-lyase deficiency. The patient was a phenotypic girl and referred to us for right-sided inguinal hernia at the age of 4 years. Biopsy of the herniated gonad showed testicular tissue. The karyotype was 46,XY. At 6 years of age, hypertension was clearly recognized and the patient was diagnosed as having 17α-hydroxylase/17,20-lyase deficiency based on the clinical and laboratory findings. Analysis of the CYP17 gene revealed a compound heterozygous mutation. One mutation was an undescribed single nucleotide deletion at codon 247 in exon 4 (CTT to CT: 247delT) and the other was a missense mutation resulting in a substitution of His to Leu at codon 373 in exon 6 (CAC to CTC: H373L), which has been previously shown to abolish both 17α-hydroxylase and 17,20-lyase activities. The functional expression study of the 247delT mutant showed that this 247delT mutation completely eliminates both 17α-hydroxylase and 17,20-lyase activities. Conclusions: Together, these results indicate that the patient is a compound heterozygote for the mutation of the CYP17 gene (247delT and H373L) and that these mutations inactivate both 17α-hydroxylase and 17,20-lyase activities and give rise to clinically manifest 17α-hydroxylase/17,20-lyase deficiency.

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A 5′-Splice Site Mutation in the Cytochrome P450 Steroid 17α-Hydroxylase Gene in 17α-Hydroxylase Deficiency

Cited by 13 publications

References 14 publications

New compound heterozygous mutations of p. Thr101Ilefs*2 and p. Thr306Ale in a child from a Chinese family with 17α-hydroxylase/17, 20-lyase deficiency

New compound heterozygous mutations of p. Thr101Ilefs*2 and p. Thr306Ale in a child from a Chinese family with 17α-hydroxylase/17, 20-lyase deficiency

Elevated Levels of Plasma Immunoassayable Aldosterone in a Mild Form of 17 Alpha-Hydroxylase/17,20-lyase Deficiency Diagnosed at the Age of 50

New Compound Heterozygous Mutation in the <i>CYP17</i> Gene in a 46,XY Girl with 17α-Hydroxylase/17,20-Lyase Deficiency

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