THU183 The Genotype-phenotype Correlation In Human 5α-reductase Type 2 Deficiency: Classified And Analysed From A SRD5A2 Structural Perspective

Abstract

Abstract Disclosure: A. Kwon: None. S. Kim: None. Y. Choi: None. H. Choi: None. H. Kim: None. The phenotype of 5α-Reductase type 2 deficiency (5αRD2) by SRD5A2 gene mutation varies, and even though there have been many attempts, the genotype-phenotype correlation has not yet still been evaluated. Recently, the crystal structure of 5α-reductase type 2 isozyme (SRD5A2) was discovered. Therefore, the present study retrospectively evaluated the genotype-phenotype correlation from a structural perspective in 19 Korean patients with 5αRD2. Additionally, variants were classified according to structural categories relative to phenotypic severity based on previously published data. The p.R227Q variant, which belongs to the NADPH binding residue mutation category, exhibited a more masculine phenotype (higher external masculinisation score) than other variants. Furthermore, compound heterozygous mutations with p.R227Q, mitigated phenotypic severity. Similarly, other mutations in this category showed mild to moderate phenotypes. Conversely, those variants categorised as structure destabilising and small to bulky residue mutations showed moderate to severe phenotypes, and the variants categorised as catalytic site and helix breaking mutations exhibited severe phenotypes. Therefore, the SRD5A2 structural approach suggested that a genotype-phenotype correlation does exist in 5αRD2. We can also conclude that the categorisation of SRD5A2 gene variants facilitates prediction of the severity of 5αRD2, its prognosis, and the management and genetic counselling of patients affected by it. Presentation: Thursday, June 15, 2023