Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia in Singapore

Background. Congenital adrenal hyperplasia arising from 21-hydroxylase deficiency is associated with mutations in the CYP21 gene on chromosome 6p. This is the first report on the mutational spectrum of the CYP21 gene in Singapore. Methods: To catalogue the mutations, ten exons of the CYP21 gene from 28 Singaporean patients were analyzed by PCR amplification and direct sequencing. Results: Common mutations in descending order were the intron 2 splice site mutation (32.7% of the alleles), the 1172N mutation (23.1% of the alleles), and the R356W mutation (19.2% of the alleles). Two potentially novel mutations were discovered: (1) duplication of 111 bp from codon 21 to codon 57 (exon 1) and (2) missense mutation (L261P, exon 7). There was generally a good genotype-phenotype correlation, allowing accurate prediction of the disease severity. Copyright (C) 2001 S. Karger AG, Basel.