A steroid 21-hydroxylase allele concomitantly carrying four disease-causing mutations is not uncommon in the swedish...

We describe a steroid 21-hydroxylase allele carrying four disease-causing mutations, viz. I173N, V282L, I237N + V238E + M240K, and the insertion of T at 308 L. The first two are established causes of partial enzyme deficiency, whereas the last two are known to result in the most severe, salt-wasting form of the disease. All four mutations are normally found in the pseudogene. This abnormal allele was found in the general Swedish population (6 out of 354 individuals), but has so far not been identified among 21-hydroxylase deficiency patients. The existence of alleles with multiple mutations illustrates the importance of segregating mutations for the correct genetic diagnosis of steroid 21-hydroxylase deficiency; an allele-specific polymerase chain reaction can be successfully employed for this purpose when families are unavailable.