title: CYP21A2 mutations in Portuguese patients with congenital adrenal hyperplasia: identification of two novel mutations and characterization of four different partial gene conversions.
abstract: More than 90% of congenital adrenal hyperplasia (CAH) cases are caused by 21-hydroxylase deficiency. In this study, the CYP21 gene was genotyped in 56 Portuguese unrelated patients with clinical symptoms of 21-hydroxylase deficiency, in a total of 112 independent alleles. CYP21A2 mutations were identified in 99.1% of the alleles. The most common point mutation was 1688G>T (25.9%). A previously unreported partial gene conversion, extending from exon 1 to 7, was found in 16.1% of the alleles, in most cases associated to the mutation 1688G>T in the other chromosome, and in patients with nonclassical CAH. Other three distinct partial gene conversions were also identified, with lower frequencies: one extends from exon 1 to 3 and the others from exons 3 to 7 and 3 to 8. Two novel mutations were identified in two salt-wasting patients: a putative splicing mutation, IVS2+5G>A, and the transition 2557C>T, that gives rise to the nonsense mutation R445X. Seven point mutations and a partial gene conversion were responsible for 88 of the studied disease causing alleles, and the overall concordance between genotype and phenotype was 92.9%. With this study the molecular basis of CAH was characterized, for the first time, in Portuguese patients, providing useful results for clinicians in terms of prediction of disease severity, genetic and prenatal counseling.
authors.affiliation: Centro de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Friães
authors.forename: Ana Toste
authors.initials: AT
authors.lastname: Rêgo
authors.forename: José Maria
authors.initials: JM
authors.lastname: Aragüés
authors.forename: Luís Francisco
authors.initials: LF
authors.lastname: Moura
authors.forename: Alice
authors.initials: A
authors.lastname: Mirante
authors.forename: Mário Rui
authors.initials: MR
authors.lastname: Mascarenhas
authors.forename: Teresa Taylor
authors.initials: TT
authors.lastname: Kay
authors.forename: Lurdes Afonso
authors.initials: LA
authors.lastname: Lopes
authors.forename: José Cidade
authors.initials: JC
authors.lastname: Rodrigues
authors.forename: Sílvia
authors.initials: S
authors.lastname: Guerra
authors.forename: Teresa
authors.initials: T
authors.lastname: Dias
authors.forename: Alberto Galvão
authors.initials: AG
authors.lastname: Teles
authors.forename: João
authors.initials: J
authors.lastname: Gonçalves
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D005260:Female; D005785:Gene Conversion; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D011174:Portugal; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D013255:Steroid 21-Hydroxylase