Author/Editor		Dolžan, Vita; Vidan-Jeras, Blanka; Preželj, Janez; Breskvar, Katja
Title		Molecular pathology of CYP21 genes-associations with HLA antigens and disease phenotypes
Type		članek
Source		Acta Chim Slov
Vol. and No.		Letnik 44, št. 1
Publication year		1997
Volume		str. 375-84
Language		eng
Abstract		CYP21 gene and a highly similar pseudogene CYP21 are located withih HLA class III region on chromosome 6p21.3. Due to high sequence similarity gene deletions, duplications and conversions are facilitated between adjacet CY21 genes. Inherited defects of CYP21 gene cause various degrees of steroid 21-hydroxylase deficiency. Partial loss of 21-hydroxylase activity results in nonclassical CAH which is clinically indistiguishable from functional hyperandrogenism (FH). Characteristic HLA haplotypes were reported to be associated with CAH in different populations. The aims of our study were to characterise mutations in CYP21 gene in CAH patients and to find out if CYP21 gene mutations also contribute to the clinical phenotype in FH. We also wished to find out if any specific HLA antigens are associated with altered CYP21 genes. 6 CAH patients, 88 FH women and 58 healthy controls were included in the study. We found causative mutations in all CAH patients. ACTH stimulation, HLA typing and molecular analysis of CUP21 gene were used to define possible carriers of CAH in FH patients. High frequency of heterozygous CUP21 deletions (7/64 patients), CYP21 deletions (15/64) and CYP21 duplications (3/64) was observed in FH patients. The frequency of CYP21 point mutations carriers was significantly higher in FH patients (4/83) than in healthy controls (0/58, p=0,048).
Descriptors		STEROID 21-MONOOXYGENASE ADRENAL HYPERPLASIA, CONGENITAL HYPERANDROGENISM CORTICOTROPIN POINT MUTATION 17-HYDROXYPROGESTERONE HLA ANTIGENS POLYMERASE CHAIN REACTION DNA, COMPLEMENTARY HAPLOTYPES