Genotype-Phenotype Correlation Analysis and Identification of a Novel Mutation in Four Unrelated Chinese Patients with 5α-Reductase Deficiency.

Objective: The 5α-reductase type 2 deficiency is mainly caused by mutations in the gene. Our study aims to investigate the gene mutations and their corresponding manifestations.

Methods: Four unrelated Chinese patients with 46, XY ambiguous genitalia were studied. Molecular genetic alterations and clinical presentations were analyzed.

Results: Five variants in the gene were identified, all highly conserved in vertebrate orthologs. The p.P251A was a novel variant, predicted to "Affect protein function" and to be "probably damaging". Combining patients' gene mutations with their external genitalia and male sexual characteristics, we found that three variants, p.Q6X, p.N193S, and p.H90Y, were associated with severe undervirilization of external genitalia, and the other two, p.G203S and p.P251A, probably retained part of the enzyme activity.

Conclusion: Mutation analysis of gene is crucial for differential diagnosis in patients with 5α-reductase type 2 deficiency. Patients' variable manifestations depend on the mutation type and residual enzyme activity. The novel variant p.P251A enlarges the spectrum of mutations.