Congenital adrenal hyperplasia (CAH) due to 21-hydroxy-lase deficiency is one of the most common autosomal recessive disorders, with an estimated carrier rate of 1 in 50 (1). The CAH phenotype depends on the degree of enzyme deficiency. The mildest deficiency leads to the non-classical disease (NC-CAH) with pseudoprecocious puberty, hirsutism, acne, and subfertility (1). The commonest mutations of CYP21A2 gene in NC-CAH (V281L, P453S) are very mild, having been associated with about 30-40 of residual enzymatic activity in vitro. However, as the severity of the disease is conditioned by the activity of the less severely affected of the two alleles, patients presenting with NC-CAH may also have one of their alleles that is severely affected. Therefore, NC-CAH may be the result of mild mutations in the "first" allele and mutations causing either complete (< 1 ), severe (1 -3) or mild (30-60) enzymatic impairment in the "second" allele. The spectrum of CYP21A2 gene mutated alleles in NC-CAH, however, has been very recently reported to be very large and the haplotypes may significantly differ in the different ethnic groups (2). The aim of this letter is to report on one additional novel mutation of CYP21A2 gene in a Sicilian girl with NC-CAH, who presented at the age of 7.8 yr owing to premature pubarche and advancement of both height and bone age. Diagnosis was assessed on the basis of the increased both baseline (64 ng/ml) and ACTH-stimulated 17-hydroxyprogesterone serum levels (124 ng/ml). Since the most common mutations do not fully explain the phe-notypes of many patients with CAH, in this patient, complete CYP21 gene was sequenced, in accordance with our methodological strategy (2).
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