title: A sequence variation in 3'UTR of CYP21A2 gene correlates with a mild form of congenital adrenal hyperplasia.
abstract: BACKGROUND
  Congenital adrenal hyperplasia (CAH) is mainly caused by the deficiency of the 21-hydroxylase enzyme coded by the CYP21A2 gene. However, some alleles in the non-classical form (NC-CAH) remain without identified mutations, suggesting the involvement of regulatory regions.
  
  
  OBJECTIVE
  Our objective was to study an allele carrying the variant *13 G>A in the 3'UTR of the CYP21A2 gene identified in some patients with a mild form of NC-CAH in order to verify the possible implication of this variation with the phenotype observed.
  
  
  METHODS
  Among all the subjects in whom the CYP21A2 gene was analyzed, 14 patients and 7 relatives heterozygous or homozygous for the *13 G>A substitution in 3'UTR were selected. Sequencing of DNA, genotyping, multiplex ligation-dependent probe amplification (MLPA), in vitro studies and bioinformatic analysis were performed.
  
  
  RESULTS
  The haplotype of the *13 G>A allele was identical in all the subjects with a monomodular structure composed by one C4A gene and one CYP21A2 gene without a second module with the CYP21A1P pseudogene. No other concomitant mutations were found in the region extending from 3 kb in the promoter and encompassing the polyadenylation signal. Both bioinformatic analysis and in vitro studies predicted an alteration of the RNA folding and expression, but no miRNA target sequences were found in this region.
  
  
  CONCLUSIONS
  The identification of a substitution in the 3'UTR of the gene associated with a mild form of NC-CAH suggests the importance of analyzing the CYP21A2 untranslated regions to better characterize and treat this subgroup of patients.
authors.affiliation: Department of Gynaecologic, Obstetric, and Paediatric Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. soara.menabo@unibo.it
authors.forename: S
authors.initials: S
authors.lastname: Menabò
authors.forename: A
authors.initials: A
authors.lastname: Balsamo
authors.forename: L
authors.initials: L
authors.lastname: Baldazzi
authors.forename: M
authors.initials: M
authors.lastname: Barbaro
authors.forename: A
authors.initials: A
authors.lastname: Nicoletti
authors.forename: V
authors.initials: V
authors.lastname: Conti
authors.forename: P
authors.initials: P
authors.lastname: Pirazzoli
authors.forename: A
authors.initials: A
authors.lastname: Wedell
authors.forename: A
authors.initials: A
authors.lastname: Cicognani
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009690:Nucleic Acid Conformation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D012333:RNA, Messenger; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase