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

Long Shyong Lee, Wei Jane Shu, Chen Ming Wu, Chia Hsing Hsieh, Su Mei Chen, Chaur Jong Hu, Wei Yi Chen, Bon chu Chung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

17α-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17α-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17α-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17α-hydroxylase/17,20-lyase deficiency in this patient.

Original languageEnglish
Pages (from-to)16-20
Number of pages5
JournalMolecular and Cellular Endocrinology
Volume249
Issue number1-2
DOIs
Publication statusPublished - Apr 25 2006

Fingerprint

Steroid 17-alpha-Hydroxylase
Cytochromes
Mixed Function Oxygenases
Mutation
Alleles
Sexual Infantilism
Genes
XY Disorders of Sex Development 46
Southeastern Asia
Mutagenesis
Functional analysis
Hypokalemia
HEK293 Cells
Enzyme activity
Missense Mutation
Rare Diseases
Site-Directed Mutagenesis
Renin
Codon
Hydrocortisone

Keywords

  • 17α-Hydroxylase deficiency
  • Congenital adrenal hyperplasia
  • CYP17
  • Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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 Jane; Wu, Chen Ming; Hsieh, Chia Hsing; Chen, Su Mei; Hu, Chaur Jong; Chen, Wei Yi; Chung, Bon chu.

In: Molecular and Cellular Endocrinology, Vol. 249, No. 1-2, 25.04.2006, p. 16-20.

Research output: Contribution to journalArticle

Lee, Long Shyong ; Shu, Wei Jane ; Wu, Chen Ming ; Hsieh, Chia Hsing ; Chen, Su Mei ; Hu, Chaur Jong ; Chen, Wei Yi ; Chung, Bon chu. / 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. In: Molecular and Cellular Endocrinology. 2006 ; Vol. 249, No. 1-2. pp. 16-20.
@article{9d4fc26723ae4c85ac5a347dd1548617,
title = "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",
abstract = "17α-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17α-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17α-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17α-hydroxylase/17,20-lyase deficiency in this patient.",
keywords = "17α-Hydroxylase deficiency, Congenital adrenal hyperplasia, CYP17, Mutation",
author = "Lee, {Long Shyong} and Shu, {Wei Jane} and Wu, {Chen Ming} and Hsieh, {Chia Hsing} and Chen, {Su Mei} and Hu, {Chaur Jong} and Chen, {Wei Yi} and Chung, {Bon chu}",
year = "2006",
month = "4",
day = "25",
doi = "10.1016/j.mce.2006.01.003",
language = "English",
volume = "249",
pages = "16--20",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - 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

AU - Lee, Long Shyong

AU - Shu, Wei Jane

AU - Wu, Chen Ming

AU - Hsieh, Chia Hsing

AU - Chen, Su Mei

AU - Hu, Chaur Jong

AU - Chen, Wei Yi

AU - Chung, Bon chu

PY - 2006/4/25

Y1 - 2006/4/25

N2 - 17α-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17α-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17α-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17α-hydroxylase/17,20-lyase deficiency in this patient.

AB - 17α-Hydroxylase deficiency is a rare disease caused by mutation of the CYP17 gene, resulting in hypertension, hypokalemia, female sexual infantilism or male pseudohermaphroditism, low blood cortisol and low plasma renin activity. Herein, we report a female Taiwanese with 17α-hydroxylase deficiency. The CYP17 genes of this patient and five members of her family were analyzed by PCR-direct sequencing. One allele of the patient contains a 9-bp (c. 1459-1467 GACTCTTTC: D487, S488, F489) deletion, which is prevalent in Southeast Asia. The other allele has a 6-bp (c. 1480-1485 AAGGTG: K494, V495) deletion and an R496L (c. 1487 G>T) missense mutation, which is a novel mutation. Site-directed mutagenesis, in vitro expression and functional analysis in HEK-293T cells showed that this novel mutation [K494_V495 Del; R496L] resulted in complete loss of 17α-hydroxylase and 17,20-lyase activity. Thus this novel mutation in the extreme C-terminus abolishes enzyme activity, and when accompanied by a 9-bp deletion at codons 487-489 in the other allele, results in 17α-hydroxylase/17,20-lyase deficiency in this patient.

KW - 17α-Hydroxylase deficiency

KW - Congenital adrenal hyperplasia

KW - CYP17

KW - Mutation

UR - http://www.scopus.com/inward/record.url?scp=33645858285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645858285&partnerID=8YFLogxK

U2 - 10.1016/j.mce.2006.01.003

DO - 10.1016/j.mce.2006.01.003

M3 - Article

C2 - 16483711

AN - SCOPUS:33645858285

VL - 249

SP - 16

EP - 20

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

IS - 1-2

ER -