The gene founder effect of two spontaneous mutations in ethnic Chinese (Taiwanese) CAH patients with 21-hydroxylase deficiency.
CYP21A2 mutations resulting from microconversions of the CYP21A1P sequence in congenital adrenal hyperplasia (CAH) commonly appear in all populations. However, it has not often been described as being due to the gene founder effect. Herein, we investigated two spontaneous mutations of IVS2+1G>A and R316X in ethnic Chinese (Taiwanese) CAH patients to determine whether they share the same haplotype of ancient origin by the analysis of sequence-specific oligonucleotide (SSO) for HLA class I B and sequence-based typing (SBT) for HLA class II DRB1 gene-typing methods. From over 200 CAH families, eight unrelated CAH patients were found and examined: five had the IVS2+1G>A mutation and three had the R316X mutation. Based on HLA typing data, five alleles in five patients with the IVS2+1G>A mutation were consistent with a shared haplotype of the B *3909-DRB1 *160201 allele, and the three alleles in the three patients with the R316X mutation were all the B *460101-DRB1 *080302 allele. The evidence indicates that the haplotype of single-base substitutions of either the IVS2+1G>A or R316X mutation came from the same allele rather than a mutational hot spot, suggesting that the gene founder effect has occurred in the Taiwanese population. This is the first report of the gene founder effect of the CYP21A2 mutation occurring in ethnic Chinese (Taiwanese) CAH patients with 21-hydroxylase deficiency.
Lee
Yann-Jinn
YJ
Department of Medical Research, Mackay Memorial Hospital, 45 Min-Sheng Road, Tanshui 251, Taipei County, Taiwan.
Tsai
Li-Ping
LP
Niu
Dau-Ming
DM
Shu
San-Ging
SG
Chao
Mei-Chyn
MC
Lee
Hsien-Hsiung
HH
D000312:Adrenal Hyperplasia, Congenital / Q000201:enzymology* / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D015235:HLA-B Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013624:Taiwan
D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D013255:Steroid 21-Hydroxylase