Clinical phenotype and mutation spectrum of the CYP21A2 gene in patients with steroid 21-hydroxylase deficiency.
Steroid 21-hydroxylase deficiency is caused by inactivating mutations in the CYP21A2 gene. This paper reports on the mutation spectrum and the genotype-phenotype correlation of 21-hydroxylase deficiency. 72 unrelated patients with congenital adrenal hyperplasia (CAH) were included. Molecular analysis of CYP21A2 was performed, via the multiplex ligation-dependent probe amplification (MLPA) analysis and sequence-specific differenzial PCR amplification of the CYP21A2 and CYP21A1P genes, using 4 pair-wise sequence-specific primers, followed by sequencing of the entire CYP21A2 gene. Large gene deletions were identified in 45 (31.3%) of the 144 unrelated CAH alleles, whereas the most frequent point mutations were intron 2 splice mutations (c.293-13A>G) (41/144, 28.5%). The MLPA analysis successfully identified 23 of 72 patients (31.9%) with single copy deletion in CYP21A2. This paper describes a rapid and accurate method for the molecular diagnosis of 21-hydroxylase deficiency, which relies on the identification of point mutations and structural rearrangements within the CYP21A2 gene.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
J-H
JH
Choi
H-Y
HY
Jin
B H
BH
Lee
J M
JM
Ko
J-J
JJ
Lee
G-H
GH
Kim
C-W
CW
Jung
J
J
Lee
H-W
HW
Yoo
D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D000483:Alleles; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007231:Infant, Newborn; D022521:Ligase Chain Reaction / Q000379:methods; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase