Phenotype-Genotype Correlation in Eight Chinese 17α-Hydroxylase/17,20 Lyase-Deficiency Patients with Five Novel Mutations of CYP17A1 Gene

Yang, Jun; Cui, Bin; Sun, Shouyue; Shi, Tieliu; Zheng, Siyuan; Bi, Yufang; Liu, Jianmin; Zhao, Yongju; Chen, Jialun; Ning, Guang; Li, Xiaoying

doi:10.1210/jc.2005-2283

Cited by 56 publications

(35 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The serum steroid profile was comparable to those previously published (8,20,24,25,28) and disclosed marked increases of B, DOC and their 18-hydroxy--derivatives -18OHB and 18OHDOC -, the so-called 17-deoxysteroids (from the "mineralocorticoid pathway") of the zona fasciculata.…”

Section: Discussionsupporting

confidence: 85%

“…Thus, failure to produce sex steroids in these patients results in sexual infantilism and primary amenorrhea in the female (46,XX) and pseudohermaphroditism in the male (46,XY) (17)(18)(19)(20). In addition, impaired production of cortisol − typical of complete 17OHD −, leads to increased ACTH secretion that stimulates overproduction of deoxycorticosterone (DOC) and corticosterone (B) − non-17-hydroxylated steroid intermediates with mineralocorticoid activity −, causing severe hypertension and hypokalemia (2,(21)(22)(23)(24)(25). Although the serum steroid profile has been extensively studied in 17OHD, systematic evaluation of the full urinary steroid metabolite (metabolome) in these patients is limited.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 85%

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

View full text Add to dashboard Cite

“…Several founder event mutations have been reported in Han populations previously, including c.1935C4A in the GAA gene, 34 c.1517_1525del in the 17OHD gene 35 and c. 1199A4G in the IVD gene. 36 This study represents the largest number of founder event mutation profiles identified so far in Han populations.…”

Section: Selection Of a Marker For Linkage Analysismentioning

confidence: 96%

Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations

Chiu

Chang²,

et al. 2012

J Hum Genet

View full text Add to dashboard Cite

The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS, gene symbol: PTS) is involved in the second step of the de novo biosynthesis of tetrahydrobiopterin (BH4), which is a vital cofactor of nitric oxide synthases and three types of aromatic amino acid hydroxylases; the latter are important enzymes in the production of neurotransmitters. We conducted a study of PTS mutations in East Asia, including Taiwan, Mainland China, Japan, South Korea, the Philippines, Thailand and Malaysia. A total of 43 mutations were identified, comprising 22 previously reported mutations and 21 new discovered mutations. Among these, the c.155A4G, c.259C4T, c. 272A4G, c.286G4A and c.84-291A4G mutations were the most common PTS mutations in East Asia, while the c.58T4C and c.243G4A mutations were, respectively, specific to Filipinos and Japanese originating from Okinawa. Further studies demonstrated that each of the mutations listed above was in linkage disequilibrium to a specific allele of polymorphic microsatellite marker, D11S1347. These results suggest the presence of founder effects that have affected these frequent mutations in East Asia populations. In this context, D11S1347 should become one of the most reliable polymorphic markers for use in prenatal diagnosis among PTPS deficient families, especially where mutations are yet to be identified.

show abstract

“…Furthermore, an analysis of 6 cases of 17OHD suggested that age of onset and hypertension severity are not consistent (14). Although there are only a few reports of 17,20-lyase activity in patients with 17OHDs with menstruation, these reports indicate that patients with 17OHD that menstruate have retained 17,20-lyase activity (8,10,15). Thus, the relationship between in vitro enzyme activity and clinical severity remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, 46,XY patients have female external genitalia with a blind-ending vagina, and their testes are found in the abdomen or inguinal canal. Some male patients exhibit ambiguous genitalia (8,9).…”

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

View full text Add to dashboard Cite

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.

show abstract

Phenotype-Genotype Correlation in Eight Chinese 17α-Hydroxylase/17,20 Lyase-Deficiency Patients with Five Novel Mutations of CYP17A1 Gene

Cited by 56 publications

References 22 publications

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

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

Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations

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

Contact Info

Product

Resources

About