Variations in the promoter of CYP21A2 gene identified in a Chinese patient with simple virilizing form of 21-hydroxylase deficiency.
OBJECTIVE
The variations in the transcriptional regulatory regions of CYP21A2 were rarely investigated in patients with 21-hydroxylase deficiency (21-OHD). The present study aims to verify that the variations in the promoter of CYP21A2 relate to the classical form of 21OHD.


METHODS
CYP21A2 was screened for mutations in 20 patients with the simple virilizing form of 21OHD, including the promoter region. The transcriptional activities of the variants in the promoter were investigated using a dual-reporter luciferase assay system and electromobility gel shift assays.


RESULTS
The heterozygous variants -447 A > G, -443InsA, -306G > C, -295T > C, -294 A > C, -283 A > G, -281T > G, -210T > C, -199C > T, -196 A > T, -126C > T, -113G > A, -110T > C, -103 A > G and -4C > T in the promoter of CYP21A2 gene were identified in a patient with simple virilizing form of 21OHD. The transcriptional activities of the promoter with the variants were reduced to 50% of the wild type.


CONCLUSIONS
We speculated that the 15 variants in the promoter of CYP21A2 combined with a compound heterozygous mutation Q318X lead to a simple virilizing form of 21OHD.
Zhang
Hui-Jie
HJ
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yang
Jun
J
Zhang
Man-Na
MN
Zhang
Wei
W
Liu
Jian-Min
JM
Wang
Wei-Qing
WQ
Ning
Guang
G
Li
Xiao-Ying
XY
D000312:Adrenal Hyperplasia, Congenital / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D002681:China; D005260:Female; D006579:Heterozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D014770:Virilism / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase