Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is an autosomal recessive disorder due to mutations in its structural gene (CYP21B). These mutations can be deletions, large gene conversions or point mutations. We have studied 99 Brazilian patients with different clinical forms of CAH representing 180 non-related chromosomes. Using Southern blot with these 180 alleles we found 16 alleles (9.7%) with large gene conversions and 7 alleles(3.2%) with deletions in the CYP21B gene, showing that deletions are an uncommon cause of the disease in our series. We have studied the frequency of 8 point mutations in the remaining 157 alleles through allele-specific polymerase chain reaction (method and controls kindly provided by Robert Wilson). Table The most frequent mutation in SW form was 12 splice, in SV form was I172N and in LO was V281L, although the latter showed a lower frequency than those found in literature. One allele resulted from a de novo I172N mutation that was found on the paternal haplotype of the patient but not in the father. Paternity was confirmed by multiple polymorphic markers. In the alleles that presented point mutations, 95% had a single mutation and 5% had two, with the following most common associations: 12 Splice+V281L and Q318X+R356W. Mutations were identified in 77% of the 180 alleles, with no identification in 13% of the SW and SV forms and 39% of the alleles in the LO form.

Table 1
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