Molecular analysis of Japanese patients with steroid 21-hydroxylase deficiency

We have designed a rapid and convenient strategy to determine nine of the m ost common mutations in the 21-hydroxylase gene (CYP21). The frequency of t he mutations was investigated in 34 Japanese patients affected with congeni tal adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency. We chara cterized 82% of the CAH chromosomes. The most frequent mutations were a CIA to G substitution in intron 2 in the salt-wasting form of the disease and an II72N in the simple virilizing form. Three ne novo mutations were found. Two homozygous mutations (S268T and N493S) were detected by direct sequenc ing of all exons of CYP21 in two siblings, who had a normal genotype at all positions screened, We successfully applied these methods for prenatal dia gnosis in one family. These procedures proved to be sensitive and rapid for the detection of the most common known mutations in the CYP21 gene and may be useful for genetic screening.