The diagnosis of non-classical (NC) 21-hydroxylase deficiency (21-OH-D) was substantiated by the finding of increased baseline and adrenocorticotropic hormone (ACTH)-stimulated 17-hydroxy-progesterone levels and was supported by molecular analyses of the CYP21A2 gene, which revealed V281L homozygosis in patient 1 and V281L/P30L compound heterozygosis in patient 2.
Conclusions This study showed that the most common alleles were IN2G-Q381X-R356W-P30L-V281L in the children with 21-OHD and asymptomatic siblings, and that the phenotype can be predicted from the genotype except for the P30L-V281L.
However, the homozygous V281L mutation in CYP21A2, the common mutation in the NC form in Caucasians, has not been described in Japanese patients, implying at least two possibilities; 1) the V281L mutation itself might be very rare in Japanese, and 2) nonclassic 21-OHD patients bearing the V281L mutation might be barely detectable by the mass-screening program, hence overlooked in Japan.