Mutation of IVS2-12A/C>G in combination with 707-714delGAGACTAC in the CYP21 gene is caused by deletion of the C4-CYP21 repeat module with steroid 21-hydroxylase deficiency

Hsien Hsiung Lee, Shwu Fen Chang, Fuu Jen Tsai, Li Ping Tsai, Ching Yu Lin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

More than 90% of the cases of congenital adrenal hyperplasia are caused by mutations of the CYP21 gene. Approximately 75% of the defective CYP21 genes are generated through intergenic recombination, termed apparent gene conversion, from the neighboring CYP21P pseudogene. Among them, mutation of the aberrant splicing donor site of IVS2 -12A/C>G at nucleotide (nt) 655 is believed to be a result derived from this mechanism and is the most prevalent case among all ethnic groups. However, mutation of 707-714delGAGACTAC rarely exists alone, although this locus is a distance of 53 nt away from IVS2 -12A/C>G. From the molecular characterization of the mutation of IVS2 - 12A/C>G combined with 707-714delGAGACTAC in patients with congenital adrenal hyperplasia, we found that it appeared to be in a 3.2- rather than a 3.7-kb fragment generated by Taq I digestion in a PCR product of the CYP21 gene. Interestingly, the 5′ end region of such a CYP21 haplotype had CYP21P-specific sequences. Our results indicate that the coexistence of these two mutations is caused by deletion of the CYP21P, XA, RP2, and C4B genes and intergenic recombination in the C4-CYP21 repeat module. Surprisingly, this kind of the haplotype of the mutated CYP21 gene has not been reported as a gene deletion.

Original languageEnglish
Pages (from-to)2726-2729
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number6
Publication statusPublished - Jun 1 2003

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Steroid 21-Hydroxylase
Genes
Mutation
Congenital Adrenal Hyperplasia
Haplotypes
Genetic Recombination
Nucleotides
Gene Conversion
Pseudogenes
Gene Deletion
Ethnic Groups
Digestion
Congenital adrenal hyperplasia due to 21 hydroxylase deficiency
Tissue Donors
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Mutation of IVS2-12A/C>G in combination with 707-714delGAGACTAC in the CYP21 gene is caused by deletion of the C4-CYP21 repeat module with steroid 21-hydroxylase deficiency. / Lee, Hsien Hsiung; Chang, Shwu Fen; Tsai, Fuu Jen; Tsai, Li Ping; Lin, Ching Yu.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 6, 01.06.2003, p. 2726-2729.

Research output: Contribution to journalArticle

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