A novel compound heterozygous mutation of K494_V495 deletion plus R496L and D487_F489 deletion in extreme C-terminus of cytochrome P450c17 causes 17α-hydroxylase deficiency

Lee, Long Shyong; Shu, Wei; Wu, Chen; Hsieh, Chia Hsing; Chen, Su Mei; Hu, Chaur Jong; Chen, Wei Yi; Chung, Bon Chu

doi:10.1016/j.mce.2006.01.003

Cited by 13 publications

(6 citation statements)

References 25 publications

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“…In this study, 14 family members from five unrelated families were genotyped; among them, seven family members were found to be heterozygous for the D487_F489 deletion of the CYP17A1 gene, six were found to be heterozygous for Y329fs, and the father of family 3 was found to be a carrier of H373L. Previous in vitro studies have shown that three mutations of the CYP17A1 gene – the D487_F489 deletion, Y329fs, and H373L – completely abolished the enzyme activity of P450c17 20–23 . However, it remains unclear as to whether steroid biosynthetic defects are present in individuals with these three mutations in only one allele of the CYP17A1 gene (i.e.…”

Section: Discussionmentioning

confidence: 87%

“…Previous in vitro studies have shown that three mutations of the CYP17A1 gene -the D487_F489 deletion, Y329fs, and H373L -completely abolished the enzyme activity of P450c17. [20][21][22][23] However, it remains unclear as to whether steroid biosynthetic defects are present in individuals with these three mutations in only one allele of the CYP17A1 gene (i.e. carriers), who are assumed to have 50% 17a-hydroxylase and 17,20-lyase activities.…”

Section: Discussionmentioning

confidence: 99%

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Identification of steroid biosynthetic defects in genotype‐proven heterozygous individuals for 17α‐hydroxylase/17,20‐lyase deficiency

Qiao

Xia

Zuo

et al. 2010

Clinical Endocrinology

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SummaryObjective P450c17 deficiency (17a-hydroxylase/17,20-lyase deficiency, 17OHD) is a rare form of congenital adrenal hyperplasia caused by CYP17A1 gene mutations. The D487_F489 deletion in exon 8 and Y329fs in exon 6 are relatively frequent mutations of the CYP17A1 gene in China that completely abolish the enzyme activity of P450c17. However, little remains known about steroid biosynthetic functions in carriers with these mutations in a single allele of the CYP17A1 gene, who are assumed to have 50% P450c17 activity. We investigated adrenal steroidogenic function in genotype-proven heterozygotes carrying such mutations in the CYP17A1 gene in vivo. Patients and design Eight patients and fourteen family members from five families with 17OHD were recruited. The mutations of the CYP17A1 gene in these individuals were screened by sequencing. The hormonal response to cosyntropin (ACTH) was evaluated in the 14 genotype-proven carriers and 45 age-and gender-matched normal controls. Results Fourteen carriers of the CYP17A1 mutation -seven with the D487_F489 deletion, six with Y329fs and one with H373L -were identified from the five families with 17OHD. Compared with normal controls, carriers showed lower basal and ACTH-stimulated cortisol levels but higher ACTH-stimulated corticosterone levels. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of the normal controls at the baseline and after cosyntropin stimulation. Similarly, the progesterone levels and the ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than those of the normal controls, both before and after ACTH stimulation. Conclusion Genotype-proven carriers of the CYP17A1 mutation who lack apparent clinical symptoms exhibit decreased adrenal 17a-hydroxylase activity and altered adrenal gland reserve for steroid biosynthesis.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Identification of steroid biosynthetic defects in genotype‐proven heterozygous individuals for 17α‐hydroxylase/17,20‐lyase deficiency

Qiao

Xia

Zuo

et al. 2010

Clinical Endocrinology

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“…Reports of CYP17 gene mutations are uncommon among patients with CAH in Asian populations studied, including Japanese, Korean, Chinese, and Thai patients [7][8][9][10][11][12][13]. We report here a Han Chinese in Taiwan with 17a-hydroxylase/ 17,20-lyase deficiency carrying a compound heterozygous mutation in the CYP17 gene.…”

Section: Introductionmentioning

confidence: 88%

A compound heterozygous mutation in the CYP17 (17α-hydroxylase/17,20-lyase) gene in a Chinese subject with congenital adrenal hyperplasia

Won¹,

Chiu

Tso

et al. 2007

Metabolism

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“…Then, the same mutation was also detected in Chinese patients from different geographic regions i.e. Hong Kong, Sichuan Province, Anhui Province, Taiwan, Shanghai, Shandong Province and Henan Province [8,[10][11][12][13][14]. The subjects of our study were from Zhejiang Province on the southeast coast of China.…”

Section: Discussionmentioning

confidence: 83%

“…Previous studies showed that most of these tumors are adrenocortical adenomas [13]. Adrenal myelolipomas, however, have also been described in few patients with 17OHD [15,16].…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis for two Chinese siblings with 17α-hydroxylase/17,20-lyase deficiency

Zhou

Wang

et al. 2011

Gynecological Endocrinology

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A novel compound heterozygous mutation of K494_V495 deletion plus R496L and D487_F489 deletion in extreme C-terminus of cytochrome P450c17 causes 17α-hydroxylase deficiency

Cited by 13 publications

References 25 publications

Identification of steroid biosynthetic defects in genotype‐proven heterozygous individuals for 17α‐hydroxylase/17,20‐lyase deficiency

Identification of steroid biosynthetic defects in genotype‐proven heterozygous individuals for 17α‐hydroxylase/17,20‐lyase deficiency

A compound heterozygous mutation in the CYP17 (17α-hydroxylase/17,20-lyase) gene in a Chinese subject with congenital adrenal hyperplasia

Clinical and genetic analysis for two Chinese siblings with 17α-hydroxylase/17,20-lyase deficiency

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