Identification of four novel mutations in the CYP21 gene in congenital adrenal hyperplasia in the Chinese

Hsien Hsiung Lee, Hsiang Tai Chao, Yann Jinn Lee, San Ging Shu, Mei Chyn Chao, Jing Mei Kuo, Bon Chu Chung

Research output: Contribution to journalArticle

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Abstract

Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. We have analyzed CYP21 gene sequences in 65 CAH families in Taiwan. All ten exons of the CYP21 gene were analyzed by differential polymerase chain reaction followed by single-strand conformation polymorphism electrophoresis and the amplification-created restriction site method. About 95% (123 chromosomes) contain mutations due to conversion of DNA sequences into its neighboring homologous pseudogene, CYP21P. Four novel mutations representing 5% of the total chromosomes have also been identified. The mutations were confirmed by sequencing an aberrant DNA fragment. These four mutations included a base change of the splicing donor site at intron 2 from GT to AT, a base substitution of C to T at codon 316, deletion of ten bases (TCCAGCTCCC) at codons 330-333 of exon 8, and duplication of 16 bases (CCTGGATGACACGGTC) at codons 393-397 of exon 9. The loss of the splicing donor site at intron 2 and the premature stop at codon 316 may result in aberrant splicing to reduce enzyme activity and a truncated protein with no enzyme activity, respectively. Likewise, both the duplication and the deletion forms create a frameshift and premature stop during translation. The resulting proteins lack the heme-binding domain and hence are expected to lose enzymatic activity. Since these mutations are not found in the neighboring CYP21P pseudogene, gene conversion should not be the cause of these novel mutations.

Original languageEnglish
Pages (from-to)304-310
Number of pages7
JournalHuman Genetics
Volume103
Issue number3
DOIs
Publication statusPublished - Oct 26 1998

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Congenital Adrenal Hyperplasia
Mutation
Codon
Genes
Exons
Pseudogenes
Introns
Steroid 21-Hydroxylase
Gene Conversion
Chromosomes, Human, Pair 5
Nonsense Codon
Enzymes
Taiwan
DNA Sequence Analysis
Electrophoresis
Chromosomes
Polymerase Chain Reaction
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Lee, H. H., Chao, H. T., Lee, Y. J., Shu, S. G., Chao, M. C., Kuo, J. M., & Chung, B. C. (1998). Identification of four novel mutations in the CYP21 gene in congenital adrenal hyperplasia in the Chinese. Human Genetics, 103(3), 304-310. https://doi.org/10.1007/s004390050821

Identification of four novel mutations in the CYP21 gene in congenital adrenal hyperplasia in the Chinese. / Lee, Hsien Hsiung; Chao, Hsiang Tai; Lee, Yann Jinn; Shu, San Ging; Chao, Mei Chyn; Kuo, Jing Mei; Chung, Bon Chu.

In: Human Genetics, Vol. 103, No. 3, 26.10.1998, p. 304-310.

Research output: Contribution to journalArticle

Lee, HH, Chao, HT, Lee, YJ, Shu, SG, Chao, MC, Kuo, JM & Chung, BC 1998, 'Identification of four novel mutations in the CYP21 gene in congenital adrenal hyperplasia in the Chinese', Human Genetics, vol. 103, no. 3, pp. 304-310. https://doi.org/10.1007/s004390050821
Lee, Hsien Hsiung ; Chao, Hsiang Tai ; Lee, Yann Jinn ; Shu, San Ging ; Chao, Mei Chyn ; Kuo, Jing Mei ; Chung, Bon Chu. / Identification of four novel mutations in the CYP21 gene in congenital adrenal hyperplasia in the Chinese. In: Human Genetics. 1998 ; Vol. 103, No. 3. pp. 304-310.
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