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Editor—Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disease, the main cause of which is steroid 21-hydroxylase (21OH) deficiency.1 The classical phenotype of the disease includes a severe salt wasting (SW) form in which both cortisol and aldosterone synthesis is impaired, and a mild form with normal aldosterone synthesis, commonly known as simple virilising (SV). In most white populations, an incidence of 1:5000 to 1:15 000 has been reported for the severe classical forms.2 The late onset form (LO), also called non-classical (NC), is characterised by the appareance of symptoms of excessive androgen activity late in life with an incidence of 1:100 to 1:1000 persons.3
The steroid 21-hydroxylase locus has a complex structure with two genes, CYP21P andCYP21, located on the short arm of chromosome 6 within the HLA class III gene region dowstream of each of the two genes encoding the fourth component of complement,C4A and C4B, respectively. Small exchanges of sequences, a process known as gene conversion, could create many of the disease causing mutated alleles by transferring some of the deleterious mutations from the pseudogene to the CYP21 gene.4 5 Owing to the complexity of the locus, complete characterisation of mutantCYP21 alleles in patients with 21OH deficiency could be performed either by direct sequencing or by a mutation scanning method, such as non-radioactive DNA single strand conformation polymorphism analysis of all exons and exon/intron junctions.6 To date, deletion and several sequence aberrations of the CYP21 gene have been reported to cause steroid 21-hydroxylase deficiency in different populations including Italians, with 10 mutations being the most frequent.7-11
In cases of other well characterised recessive diseases, such as phenylketonuria and cystic fibrosis, clear heterogeneity of distribution of the relative frequencies of the disease mutation has been …