E. Dondi et al., MOLECULAR ANALYSIS OF CYP21 GENE-MUTATIONS CARRIED ON HLA-B14 POSITIVE HAPLOTYPES, European journal of immunogenetics, 21(5), 1994, pp. 341-350
HLA-B14 positive haplotypes have increased frequencies in a group of p
atients with puberty disorders, IgA deficiency and cancer of the ovary
. Clinical investigations demonstrated that all these patients have hi
gh values of 170H progesteron after the ACTH test which suggests an al
terated function of 21 hydroxylase enzyme. In order to investigate whe
ther these B14 positive haplotypes carry the same CYP21 mutation in th
e various diseases and controls, we have amplified by polymerase chain
reaction (PCR) the sections of CYP21B gene which include amino acid p
ositions 172 and 281 where typical mutations are known to occur in 21
hydroxylase deficiency. The presence or absence of the defined mutatio
ns was tested by oligonucleotide hybridization using oligonucleotides,
labelled with DIG-ddUTP, designed to hybridize with the mutated or wi
th the normal sequence. It was found that regardless of whether the su
bject tested was a patient or st healthy control the mutation at posit
ion 281 was found in all cases carrying HLA-B14, DR1 haplotype. Intere
stingly, this mutation does not seem to be in association with HLA-B14
, DR7 haplotype. These findings suggest that CYP21 gene plays a role i
n all these differing diseases although it must be stressed that there
may be alternative explanations for the observed data.