The degree of external genitalia virilization in girls with 21-hydroxylase deficiency appears to be influenced by the CAG repeats inthe androgen receptor gene.
Rocha RO, Billerbeck AE, Pinto EM, Melo KF, Lin CJ, Longui CA, Mendonca BB, Bachega TA.
Laboratório de Hormônios e Genética Molecular-LIM/42, Unidade deEndocrinologia do Desenvolvimento, Disciplina de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Womenwith 21-hydroxylase deficiency present much variability in external genitalia virilization, even among those with similar impairments of 21-hydroxylase (21OH) activity.
To evaluate ifthe 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 21OHactivity.
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 Aand B, which confer total and severe impairment of 21OH activity, respectively.
The inactivation pattern of the X-chromosome was studied through genomic DNA digestion with Hpa II. TheCAG repeat region was amplified by polymerase chain reaction (PCR) and analysed by GeneScan.
The nCAG and the frequency of severe skewed X-inactivation did not differ between normalwomen 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 nCAGmedian 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...