Clinical, hormonal, and genetic characteristics of 5α-RD2 deficiency in 103 Chinese patients

5α-Reductase type 2 (5α-RD2) deficiency causes variable degrees of undervirilization in patients. The correlation between genotype and phenotype is unclear. We retrospectively evaluated 103 patients with 46,XY disorders of sex development who were diagnosed with 5α-RD2 deficiency. The prevalence of female sex assignment (P = 0.008) and the incidences of cryptorchidism (P = 0.0003) and bifid scrotum (P = 0.0002) in the non-p.R227Q variant group were higher, but there were no significant differences in the incidences of hypospadias or isolated microphallus. The external masculinization score (EMS) in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant group (P = 0.019) or compound heterozygous p.R227Q variant group (P = 0.013). The level of AMH in the non-p.R227Q variant group was lower than that in the homozygous p.R227Q variant group (P < 0.001) or compound p.R227Q heterozygous variant group (P = 0.006). The testosterone:dihydrotestosterone (T:DHT) ratio of the homozygous p.R227Q variant group was higher than that of the non-p.R227Q variant group (P = 0.018) or compound heterozygous p.R227Q variant group (P = 0.029). Twenty-three reported pathogenic variants and 11 novel SRD5A2 variants were identified. Compared with non-p.R227Q patients, p.R227Q patients exhibited higher EMS and AMH expression, lower prevalence of female sex assignment and lower incidences of cryptorchidism and bifid scrotum. We identified 23 reportedly pathogenic SRD5A2 variants and 11 novel SRD5A2 variants that led to 5α-RD2 deficiency. We established a genotype-phenotype correlation, and patients with p.R227Q showed a relatively mild phenotype.