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.
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.
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.