Novel missense mutations, GCC [Ala306] - > GTC [Val] and ACG [Thr318] - > CCG [Pro], in the CYP11B1 gene cause steroid 11β-hydroxylase deficiency in the Chinese

Hsien Hsiung Lee, Ging Shing Won, Hsiang Tai Chao, Yann Jinn Lee, Bon Chu Chung

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: Steroid 11β-hydroxylase (CYP11B1) deficiency, an autosomal recessive inherited disease, accounts for 5-8% of congenital adrenal hyperplasia (CAH). It is mainly caused by mutations of nucleotide substitutions in the coding region. Patients and Methods: The study reports on a 9-year-old Chinese boy who presented with a bone age of 16 years, an enlarged penis, an accelerated growth rate since early childhood and hypertension (160-170/100-110 mmHg) for 3 years. Because it shares 95% sequence homology with aldosterone synthetase (CYP11B2), we developed gene-specific primers for differential PCR amplification of the CYP11B1 gene. The secondary PCR products of nine exons of the CYP11B1 gene were then subjected to single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The serum hormone levels were also determined. Results: We found that the boy diagnosed with CAH due to 11β-hydroxylase deficiency carried mutations of A306V (GCC- > GTC) and T318P (ACG- > CCG) in two respective chromosomes. The hormone assay showed that the 11-deoxycortisol level was higher (667 nmol/l) than normal and was further increased after ACTH stimulation (1206 nmol/l). Conclusions: These two mutations have not previously been described in the CYP11B1 gene. The discovery of these two novel mutations increases our knowledge of CAH caused by 11β-hydroxylase deficiency.

Original languageEnglish
Pages (from-to)418-422
Number of pages5
JournalClinical Endocrinology
Volume62
Issue number4
DOIs
Publication statusPublished - Apr 1 2005

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Steroid 11-beta-Hydroxylase
Missense Mutation
Congenital Adrenal Hyperplasia
Mutation
Genes
Mixed Function Oxygenases
Cytochrome P-450 CYP11B2
Cortodoxone
Hormones
Polymerase Chain Reaction
Gene Amplification
Penis
Ligases
Sequence Homology
Aldosterone
DNA Sequence Analysis
Adrenocorticotropic Hormone
Exons
Nucleotides
Chromosomes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Novel missense mutations, GCC [Ala306] - > GTC [Val] and ACG [Thr318] - > CCG [Pro], in the CYP11B1 gene cause steroid 11β-hydroxylase deficiency in the Chinese. / Lee, Hsien Hsiung; Won, Ging Shing; Chao, Hsiang Tai; Lee, Yann Jinn; Chung, Bon Chu.

In: Clinical Endocrinology, Vol. 62, No. 4, 01.04.2005, p. 418-422.

Research output: Contribution to journalArticle

Lee, Hsien Hsiung ; Won, Ging Shing ; Chao, Hsiang Tai ; Lee, Yann Jinn ; Chung, Bon Chu. / Novel missense mutations, GCC [Ala306] - > GTC [Val] and ACG [Thr318] - > CCG [Pro], in the CYP11B1 gene cause steroid 11β-hydroxylase deficiency in the Chinese. In: Clinical Endocrinology. 2005 ; Vol. 62, No. 4. pp. 418-422.
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abstract = "Objective: Steroid 11β-hydroxylase (CYP11B1) deficiency, an autosomal recessive inherited disease, accounts for 5-8{\%} of congenital adrenal hyperplasia (CAH). It is mainly caused by mutations of nucleotide substitutions in the coding region. Patients and Methods: The study reports on a 9-year-old Chinese boy who presented with a bone age of 16 years, an enlarged penis, an accelerated growth rate since early childhood and hypertension (160-170/100-110 mmHg) for 3 years. Because it shares 95{\%} sequence homology with aldosterone synthetase (CYP11B2), we developed gene-specific primers for differential PCR amplification of the CYP11B1 gene. The secondary PCR products of nine exons of the CYP11B1 gene were then subjected to single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The serum hormone levels were also determined. Results: We found that the boy diagnosed with CAH due to 11β-hydroxylase deficiency carried mutations of A306V (GCC- > GTC) and T318P (ACG- > CCG) in two respective chromosomes. The hormone assay showed that the 11-deoxycortisol level was higher (667 nmol/l) than normal and was further increased after ACTH stimulation (1206 nmol/l). Conclusions: These two mutations have not previously been described in the CYP11B1 gene. The discovery of these two novel mutations increases our knowledge of CAH caused by 11β-hydroxylase deficiency.",
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AU - Won, Ging Shing

AU - Chao, Hsiang Tai

AU - Lee, Yann Jinn

AU - Chung, Bon Chu

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AB - Objective: Steroid 11β-hydroxylase (CYP11B1) deficiency, an autosomal recessive inherited disease, accounts for 5-8% of congenital adrenal hyperplasia (CAH). It is mainly caused by mutations of nucleotide substitutions in the coding region. Patients and Methods: The study reports on a 9-year-old Chinese boy who presented with a bone age of 16 years, an enlarged penis, an accelerated growth rate since early childhood and hypertension (160-170/100-110 mmHg) for 3 years. Because it shares 95% sequence homology with aldosterone synthetase (CYP11B2), we developed gene-specific primers for differential PCR amplification of the CYP11B1 gene. The secondary PCR products of nine exons of the CYP11B1 gene were then subjected to single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The serum hormone levels were also determined. Results: We found that the boy diagnosed with CAH due to 11β-hydroxylase deficiency carried mutations of A306V (GCC- > GTC) and T318P (ACG- > CCG) in two respective chromosomes. The hormone assay showed that the 11-deoxycortisol level was higher (667 nmol/l) than normal and was further increased after ACTH stimulation (1206 nmol/l). Conclusions: These two mutations have not previously been described in the CYP11B1 gene. The discovery of these two novel mutations increases our knowledge of CAH caused by 11β-hydroxylase deficiency.

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