A novel homozygous nonsense mutations E135* in the type II 3beta-hydroxysteroid dehydrogenase gene in a girl with salt-losing congenital adrenal hyperplasia. Mutations in brief no. 168. Online.

Mutations in the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) type II gene have been reported in a small number of affected females. We report a 46,XX girl born to consanguineous parents from Chile. At birth, she had normal but hyperpigmented female external genitalia. At 60 days she presented salt loss. At 20 months, the diagnosis of classic salt-losing 3beta-HSD deficiency was made based on an elevated serum 17-hydroxpregnenolone concentration and a high 17 hydroxypregnenolone/17-hydroxyprogesterone ratio. Genomic DNA was amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis and directly sequenced. A novel homozygous E135* mutation was found in the 3beta-HSD type II gene of the patient while her parents were heterozygotes. This novel nonsense homozygous E135* mutation led to encode a predicted truncated 134 amino acid protein instead of the native 371 amino acid 3beta-HSD type II protein. This predicted product is consistent with the severe 3beta-HSD deficiency in this girl.