Impact of Genome Complexity of the CYP21A2 Gene on Adrenal Steroidogenesis

研究成果: 雜誌貢獻文章

摘要

Steroidogenesis in the adrenal cortex generates mineralocorticoids, glucocorticoids, and androgens, all of which are mediated by numerous enzymes and regulatory factors from the precursor, cholesterol. Defective adrenal steroidogenesis disorders include Addison's disease, congenital adrenal hyperplasia (CAH), and Cushing syndrome. CAH is one of the most common inborn errors of metabolism, causing impaired adrenal cortisol and aldosterone production with increased androgen secretion. P450c21-hydroxylase deficiency caused by inactivating mutations in the 21-hydroxylase gene (CYP21A2) accounts for 95% of mutations in these CAH patients. Notably, pseudogene-derived CYP21A2 lesions including mutations or large rearrangements represent the majority of CAH alleles, and the combination of altered alleles reflects the phenotypic severity of CAH, either simple virilizing or salt-wasting classical form. In addition, gene copy number variation has been correlated to disease susceptibility at the post-genomic era. This article reviews the complex organization of the CYP21 locus and its possible impact on phenotypic expression in CAH patients, emphasizing the concept of haplotype variations for CAH patients.

原文英語
頁(從 - 到)317-319
頁數3
期刊Journal of Experimental and Clinical Medicine(Taiwan)
4
發行號6
DOIs
出版狀態已發佈 - 十二月 2012

指紋

Congenital Adrenal Hyperplasia
Genome
Genes
Mutation
Androgens
Alleles
Steroid 21-Hydroxylase
Addison Disease
Inborn Errors Metabolism
Mineralocorticoids
Pseudogenes
Gene Dosage
Cushing Syndrome
Adrenal Cortex
Disease Susceptibility
Mixed Function Oxygenases
Aldosterone
Haplotypes
Glucocorticoids
Hydrocortisone

ASJC Scopus subject areas

  • Medicine(all)

引用此文

@article{7d221ab5e4f94b228493d251ab8e4226,
title = "Impact of Genome Complexity of the CYP21A2 Gene on Adrenal Steroidogenesis",
abstract = "Steroidogenesis in the adrenal cortex generates mineralocorticoids, glucocorticoids, and androgens, all of which are mediated by numerous enzymes and regulatory factors from the precursor, cholesterol. Defective adrenal steroidogenesis disorders include Addison's disease, congenital adrenal hyperplasia (CAH), and Cushing syndrome. CAH is one of the most common inborn errors of metabolism, causing impaired adrenal cortisol and aldosterone production with increased androgen secretion. P450c21-hydroxylase deficiency caused by inactivating mutations in the 21-hydroxylase gene (CYP21A2) accounts for 95{\%} of mutations in these CAH patients. Notably, pseudogene-derived CYP21A2 lesions including mutations or large rearrangements represent the majority of CAH alleles, and the combination of altered alleles reflects the phenotypic severity of CAH, either simple virilizing or salt-wasting classical form. In addition, gene copy number variation has been correlated to disease susceptibility at the post-genomic era. This article reviews the complex organization of the CYP21 locus and its possible impact on phenotypic expression in CAH patients, emphasizing the concept of haplotype variations for CAH patients.",
keywords = "Adrenal steroidogenesis, Congenital adrenal hyperplasia, Cytochrome P450 enzymes, Pseudogene CYP21A1P",
author = "Chang, {Shwu Fen}",
year = "2012",
month = "12",
doi = "10.1016/j.jecm.2012.10.005",
language = "English",
volume = "4",
pages = "317--319",
journal = "Journal of Experimental and Clinical Medicine",
issn = "1878-3317",
publisher = "Elsevier Taiwan LLC",
number = "6",

}

TY - JOUR

T1 - Impact of Genome Complexity of the CYP21A2 Gene on Adrenal Steroidogenesis

AU - Chang, Shwu Fen

PY - 2012/12

Y1 - 2012/12

N2 - Steroidogenesis in the adrenal cortex generates mineralocorticoids, glucocorticoids, and androgens, all of which are mediated by numerous enzymes and regulatory factors from the precursor, cholesterol. Defective adrenal steroidogenesis disorders include Addison's disease, congenital adrenal hyperplasia (CAH), and Cushing syndrome. CAH is one of the most common inborn errors of metabolism, causing impaired adrenal cortisol and aldosterone production with increased androgen secretion. P450c21-hydroxylase deficiency caused by inactivating mutations in the 21-hydroxylase gene (CYP21A2) accounts for 95% of mutations in these CAH patients. Notably, pseudogene-derived CYP21A2 lesions including mutations or large rearrangements represent the majority of CAH alleles, and the combination of altered alleles reflects the phenotypic severity of CAH, either simple virilizing or salt-wasting classical form. In addition, gene copy number variation has been correlated to disease susceptibility at the post-genomic era. This article reviews the complex organization of the CYP21 locus and its possible impact on phenotypic expression in CAH patients, emphasizing the concept of haplotype variations for CAH patients.

AB - Steroidogenesis in the adrenal cortex generates mineralocorticoids, glucocorticoids, and androgens, all of which are mediated by numerous enzymes and regulatory factors from the precursor, cholesterol. Defective adrenal steroidogenesis disorders include Addison's disease, congenital adrenal hyperplasia (CAH), and Cushing syndrome. CAH is one of the most common inborn errors of metabolism, causing impaired adrenal cortisol and aldosterone production with increased androgen secretion. P450c21-hydroxylase deficiency caused by inactivating mutations in the 21-hydroxylase gene (CYP21A2) accounts for 95% of mutations in these CAH patients. Notably, pseudogene-derived CYP21A2 lesions including mutations or large rearrangements represent the majority of CAH alleles, and the combination of altered alleles reflects the phenotypic severity of CAH, either simple virilizing or salt-wasting classical form. In addition, gene copy number variation has been correlated to disease susceptibility at the post-genomic era. This article reviews the complex organization of the CYP21 locus and its possible impact on phenotypic expression in CAH patients, emphasizing the concept of haplotype variations for CAH patients.

KW - Adrenal steroidogenesis

KW - Congenital adrenal hyperplasia

KW - Cytochrome P450 enzymes

KW - Pseudogene CYP21A1P

UR - http://www.scopus.com/inward/record.url?scp=84871457602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871457602&partnerID=8YFLogxK

U2 - 10.1016/j.jecm.2012.10.005

DO - 10.1016/j.jecm.2012.10.005

M3 - Article

AN - SCOPUS:84871457602

VL - 4

SP - 317

EP - 319

JO - Journal of Experimental and Clinical Medicine

JF - Journal of Experimental and Clinical Medicine

SN - 1878-3317

IS - 6

ER -