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.
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.
Lee
Hsien-Hsiung
HH
King Car Food Industrial Co., Yuan-Shan Research Institute, Ilan 264, Taiwan, Republic of China. hhlee@ms2.kingcar.com.tw
Chang
Shwu-Fen
SF
Tsai
Fuu-Jen
FJ
Tsai
Li-Ping
LP
Lin
Ching-Yu
CY
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000483:Alleles; D015935:Complement C4b / Q000235:genetics; D005136:Eye Proteins; D019204:GTP-Binding Proteins; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011544:Pseudogenes; D011993:Recombinant Fusion Proteins / Q000235:genetics; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins; C072178:RP2 protein, human; D011993:Recombinant Fusion Proteins; D015935:Complement C4b; D013255:Steroid 21-Hydroxylase; D019204:GTP-Binding Proteins