Characterization of the CYP21 Gene 5' Flanking Region in Patients Affected by 21-OH Deficiency

Contract grant sponsor: MURST; Contract grant number: Piani di potenziamento della rete scientifica etecnologica-Cluster 03Communicated byUlf LandegrenIn order to test the hypothesis that mutations in the 5’ non-coding region of CYP21 genecould contribute to the various spectrum of disease presentation due to 21-OH deficiency,the 400bp nucleotide sequence upstream of the ATG codon of CYP21 gene has beencharacterized in 28 CAH patients who have previously been genotyped by screening for theten most frequent CYP21 mutations. Six specific sequence variations (–4C →T, –73C →T, –295T →C, –294A →C, –283A →G, –281T →G) have been identified in this region of CYP21gene in 3 out of 28 21-OH deficient patients for whom the coding region mutations have beenpreviously identified. Three of these mutations, –295T →C, –294A →C, –283A →G, areapparently generated by a gene-conversion event, thus giving first evidence that thismechanism also applies to the 5’ untranslated region of CYP21 gene in 21-OH deficiency.Four other sequence changes, identified at nucleotide position –279, –331, –350 and –353,could be referred to as normal since they are present also in healthy subjects. It may not beexcluded that some of the newly-identified single nucleotide changes in the regulatory regioncould have a modulatory effect on the CYP21 gene transcriptional activity thus affecting theclinical outcome.