ClinVar

In 3 affected members of a nonconsanguineous Brazilian family with combined 17-alpha-hydroxylase/17,20-lyase deficiency (202110), Martin et al. (2003) identified compound heterozygosity for mutations in the CYP17A1 gene: a 6535G-A transition in exon 6, resulting in an arg362-to-cys (R362C) substitution, and a 7564T-C transition in exon 7, resulting in a trp406-to-arg substitution (W406R; 609300.0024). In a note added in proof, the authors stated that both the R362C and W406R mutations independently result in functionally inactive proteins.

In a molecular genetic analysis of 24 subjects from 19 families with 17-hydroxylase deficiency in Brazil, Costa-Santos et al. (2004) found that the R362C mutation accounted for 32% of the mutant alleles. The R362C mutation was completely inactive when studied in COS-7 cells and yeast microsomes; however, phenotypic features varied among subjects. The authors found mutations R362C and W406R principally in families with Portuguese and Spanish ancestry, respectively, suggesting that 2 independent founder effects contribute to the increased prevalence of 17-hydroxylase deficiency in Brazil.