Data Sheet 1_Clinical characteristics and genotype–phenotype correlation analysis in 279 patients with 5α-reductase type 2 deficiency.pdf

Consanguinity was strongly associated with homozygous mutations (P < 0.001), and patients with homozygous mutations had significantly more severe undermasculinization than compound heterozygotes (P = 0.011). p.R246Q, p.G203S, and p.R246W were significantly associated with a higher likelihood of hypospadias; p.R227Q was significantly associated with a lower likelihood of cryptorchidism and scrotal abnormalities. Frameshift mutations were associated with impaired pubertal development (P = 0.013).

Homozygous carriers were diagnosed significantly later than heterozygotes (P = 0.029), and serum FSH levels positively correlated with phenotypic severity (P = 0.021).</p>Conclusion<p>We verified that the genotype–phenotype correspondence is non-linear and multifactorial, jointly modulated by mutation subtype, residual enzyme activity, endocrine axis status, geographical disparities, consanguinity, and regional medical resource availability.

These findings provide more reliable evidence for clinical diagnosis, treatment, and prognosis assessment.</p>