Low frequency of the CYP21A2 deletion in ethnic Chinese (Taiwanese) patients with 21-hydroxylase deficiency.
Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder which causes more than 90% of CAH cases due to defects in the steroid 21-hydroxylase gene (CYP21A2). The frequency of large mutations was determined in 200 ethnic Chinese (i.e., Taiwanese) CAH patients belonging to 200 families with different clinical forms of CYP21A2 deficiency over 10 years of molecular diagnoses. For a large-gene deletion (or conversion) and the CYP21A2 deletion identification, a PCR product covering the TNXB gene and the 5'-end of the CYP21A2 gene with TaqI endonuclease digestion was analyzed by electrophoresis on agarose gels. For CYP21A2 mutational analysis, secondary PCR amplification of the amplification-created restriction site method was applied. From the results of the analysis, we found that large-gene deletions (or conversions) occurred in 7.5% of the alleles including three different types of the chimeric CYP21A1P/CYP21A2 genes and the haplotype of IVS2-12A/C>G in combination with the 707-714del mutation (without the P30L mutation). The CYP21A2 deletion occurred in 2.0% of the alleles which contained three types of the chimeric TNXA/TNXB genes with two novel ones. We concluded that the CYP21A2 deletion in the ethnic Chinese (Taiwanese) patients exhibits a low occurrence, with the haplotype of the IVS2-12A/C>G in combination with the 707-714del mutation (without the P30L mutation) being prevalent among large gene deletions or conversions.
Lee
Hsien-Hsiung
HH
Department of Medical Research, Mackay Memorial Hospital, 45 Min-Sheng Road, Tanshui 251, Taipei County, Taiwan. hhlee@ms1.mmh.org.tw
Lee
Yann-Jinn
YJ
Wang
Yu-Mei
YM
Chao
Hsiang-Tai
HT
Niu
Dau-Ming
DM
Chao
Mei-Chyn
MC
Tsai
Fuu-Jen
FJ
Lo
Fu-Sung
FS
Lin
Shio-Jean
SJ
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D016133:Polymerase Chain Reaction; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013624:Taiwan
D013255:Steroid 21-Hydroxylase; C042367:endodeoxyribonuclease TaqII; D015252:Deoxyribonucleases, Type II Site-Specific