title: Lack of genotypephenotype correlation in congenital adrenal hyperplasia due to a CYP21A2-like gene.
abstract: BACKGROUND
  Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, encoded by CYP21A2 gene, is an autosomal recessive disorder. The CYP21A2 gene, localized in a genetic unit defined RCCX module, is considered one of the most polymorphic of human genes.
  
  
  OBJECTIVE
  We considered new evidences about the presence of a RCCX trimodular haplotype with a CYP21A2-like gene to explain the lack of a genotype-phenotype correlation in individuals of two different families.
  
  
  METHODS
  To verify gene duplication we used Multiplex Ligation Probe-Dependent Amplifications (MLPA) and to confirm the presence of a CYP21A2-like gene downstream TNXA gene we used previously described amplification and restriction strategy followed by the sequencing of the CYP21A2 gene downstream TNXB gene.
  
  
  RESULTS
  The amplification strategy and restriction analysis of CYP21A1P/CYP21A2-TNXA PCR product in association with MLPA assay and sequencing of CYP21A2 gene downstream TNXB were able to identify the presence of the CYP21A2-like gene in healthy subjects of the two families, wherein the direct sequencing of CYP21A2 gene showed genotypes correlated to pathological phenotypes.
  
  
  CONCLUSIONS
  The strategy suggested is useful to facilitate molecular testing in CAH patients, considering the new evidence about possible different haplotypes.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy. Electronic address: leccese.angelica@tiscali.it.
authors.forename: A
authors.initials: A
authors.lastname: Leccese
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Longo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Dimatteo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: De Girolamo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Trunzo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: D'Andrea
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Bafunno
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Margaglione
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Santacroce
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase
keywords: 21-hydroxylase deficiency (21OHD); CYP21A2-like gene; Genotype–phenotype correlation; Molecular diagnosis