Mutational characterization of steroid 21-hydroxylase gene in Portuguese patients with congenital adrenal hyperplasia.
Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common inherited disorder of adrenal hormone biosynthesis due to mutations in the 21-hydroxylase gene, CYP21A2. Genotyping for ten of the most frequent mutations was performed in 84 Portuguese CAH patients: 10 salt-wasters, 6 simple-virilizers and 68 non-classical patients. The patients were diagnosed by a level of 17-hydroxyprogesterone above 10 ng/ml either in basal conditions or after an ACTH 0,25 mg IV Test. A variety of genotyping techniques were used to detect these ten mutations. CYP21A2 mutations were detected in 91.7% (77/84) of the patients. The frequency of alleles carrying two or more CYP21A2 mutations (9.5% - 16/168) is higher than in other populations. The most frequent mutations identified in our population were V281L (41.7%) and deletions/conversions involving the promoter region of the CYP21A2 gene (28.3%). A decreased frequency of IVS2-12C/A>G mutation (5.6%) was the most characteristic feature of our population. This study allow the characterization of the mutational spectrum of CAH patients, mainly non-classical CAH, with 21-hydroxylase deficiency from Portugal showing specific genetic features of this population which reveals differences with worldwide countries.
Department of Genetics, Faculty of Medicine, University of Porto, Porto, Portugal.
C J
CJ
Marques
D
D
Pignatelli
B
B
Carvalho
J
J
Barceló
A C
AC
Almeida
S
S
Fernandes
S F
SF
Witchel
M
M
Sousa
M J
MJ
Oliveira
P
P
Freitas
M
M
Fontoura
D
D
Carvalho
A
A
Barros
F
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Carvalho
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011174:Portugal / Q000453:epidemiology; D011401:Promoter Regions, Genetic; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D019326:17-alpha-Hydroxyprogesterone; D013255:Steroid 21-Hydroxylase