title: The degree of external genitalia virilization in girls with 21-hydroxylase deficiency appears to be influenced by the CAG repeats in the androgen receptor gene.
abstract: BACKGROUND
  Women with 21-hydroxylase deficiency present much variability in external genitalia virilization, even among those with similar impairments of 21-hydroxylase (21OH) activity.
  
  
  OBJECTIVE
  To evaluate if the number of CAG (nCAG) repeats of the androgen receptor gene influences the degree of external genitalia virilization in women with CYP21A2 mutations, grouped according to impairment of 21OH activity.
  
  
  METHODS
  The nCAG was determined in 106 congenital adrenal hyperplasia (CAH) patients and in 302 controls. The patients were divided, according to their CYP21A2 genotypes, into Groups A and B, which confer total and severe impairment of 21OH activity, respectively.
  
  
  METHODS
  The inactivation pattern of the X-chromosome was studied through genomic DNA digestion with Hpa II. The CAG repeat region was amplified by polymerase chain reaction (PCR) and analysed by GeneScan.
  
  
  RESULTS
  The nCAG and the frequency of severe skewed X-inactivation did not differ between normal women and patients. The nCAG median in genotype A was 20.7 (IQR 2.3) for Prader I + II, 22.5 (3.6) for Prader III and 21 (2.9) for Prader IV + V (P < 0.05 for Prader III and Prader IV + V). The nCAG median in genotype B was 21.3 (1.1) for Prader I + II, 20.5 (2.9) for Prader III and 22 (2.8) for Prader IV + V (P > 0.05). A significant difference was found regarding the nCAG median in patients presenting Prader III from genotypes A and B.
  
  
  CONCLUSIONS
  We observed great variability in the degree of external genitalia virilization in both CYP21A2 genotypes, and we showed that the CAG repeats of the androgen receptor gene influences this phenotypic variability.
authors.affiliation: Laboratório de Hormônios e Genética Molecular-LIM/42, Unidade de Endocrinologia do Desenvolvimento, Disciplina de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Rosana O
authors.initials: RO
authors.lastname: Rocha
authors.forename: Ana Elisa C
authors.initials: AE
authors.lastname: Billerbeck
authors.forename: Emília M
authors.initials: EM
authors.lastname: Pinto
authors.forename: Karla F S
authors.initials: KF
authors.lastname: Melo
authors.forename: Chin J
authors.initials: CJ
authors.lastname: Lin
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Longui
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Tânia A S S
authors.initials: TA
authors.lastname: Bachega
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism; D018911:Trinucleotide Repeats / Q000235:genetics*; D014770:Virilism / Q000235:genetics*