title: [Simple virilizing forms of congenital adrenal hyperplasia: adaptation and prospective validation of the molecular screening].
abstract: OBJECTIVE
  Congenital Adrenal Hyperplasia (CAH) is not an infrequent genetic disorder for which mutation-based analysis for CYP21A2 gene is a useful tool. Contrarily to salt-wasting forms the basic mutation screening accounts only for 83% of simple virilising (SV) phenotypes. Rare alleles with a local distribution not included in the basic panel may reduce its diagnostic accuracy. Our aim is to explore underlying prevalent mutations among our partially characterised SV forms and to evaluate their potential impact in the mutation screening.
  
  
  METHODS
  Preliminary study: CYP21A2 gene sequencing in 13 SV patients partially characterised. Retrospective targeted study: 2,097 DNA samples (561 patients) were re-analysed for p.R426H mutation. Prospective targeted study: incorporation of the p.R426H mutation to the initial exploration of CAH in 1,041 DNA samples to validate this extended screening.
  
  
  RESULTS
  p.R426H mutation was detected in five patients in the preliminary analysis and in ten more during targeted studies. A frequency for this mutation was 0.71% in the whole group and 7.14% in SV forms. Associated haplotypes were identical thus suggesting a preferential dissemination. The observed phenotypes correlated and confirmed the moderate-to-severe effect on the enzymatic activity.
  
  
  CONCLUSIONS
  Our data relative to allelic frequency of the p.R426H mutation and its strong association to SV forms justify the incorporation of the p.R426H mutation into the basic screening panel because of the significant improvement in the initial characterization of affected patients, especially among those with SV forms. Two new cases detected remark the usefulness of this novel approach.
authors.affiliation: Laboratorio de Diagnóstico Molecular, Hospital General Universitario Gregorio Marañón, Madrid, España. jsantome.hgugm@salud.madrid.org
authors.forename: José Luis
authors.initials: JL
authors.lastname: Santomé Collazo
authors.forename: Ana
authors.initials: A
authors.lastname: Cirujano Segura
authors.forename: Belén
authors.initials: B
authors.lastname: Ferreiro Fernández
authors.forename: Consolación
authors.initials: C
authors.lastname: Casado Fúnez
authors.forename: Rafael
authors.initials: R
authors.lastname: Muñoz-Pacheco
authors.forename: Begoña
authors.initials: B
authors.lastname: Ezquieta Zubicaray
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010375:Pedigree; D011446:Prospective Studies; D014770:Virilism / Q000235:genetics*