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The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective

The phenotype of the 5α-reductase type 2 deficiency (5αRD2) by the SRD5A2 gene mutation varies, and although there have been many attempts, the genotype-phenotype correlation still has not yet been adequately evaluated. Recently, the crystal structure of the 5α-reductase type 2 isozyme (SRD5A2) has...

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Autores principales: Seo, Jieun, Shin, Saeam, Kim, Sang-woon, Kim, Su Jin, Lee, Myeongseob, Song, Kyungchul, Suh, Junghwan, Lee, Seung-Tae, Lee, Yong Seung, Chae, Hyun Wook, Kim, Ho-Seong, Choi, Jong Rak, Han, Sangwon, Kwon, Ahreum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966410/
https://www.ncbi.nlm.nih.gov/pubmed/36834714
http://dx.doi.org/10.3390/ijms24043297
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author Seo, Jieun
Shin, Saeam
Kim, Sang-woon
Kim, Su Jin
Lee, Myeongseob
Song, Kyungchul
Suh, Junghwan
Lee, Seung-Tae
Lee, Yong Seung
Chae, Hyun Wook
Kim, Ho-Seong
Choi, Jong Rak
Han, Sangwon
Kwon, Ahreum
author_facet Seo, Jieun
Shin, Saeam
Kim, Sang-woon
Kim, Su Jin
Lee, Myeongseob
Song, Kyungchul
Suh, Junghwan
Lee, Seung-Tae
Lee, Yong Seung
Chae, Hyun Wook
Kim, Ho-Seong
Choi, Jong Rak
Han, Sangwon
Kwon, Ahreum
author_sort Seo, Jieun
collection PubMed
description The phenotype of the 5α-reductase type 2 deficiency (5αRD2) by the SRD5A2 gene mutation varies, and although there have been many attempts, the genotype-phenotype correlation still has not yet been adequately evaluated. Recently, the crystal structure of the 5α-reductase type 2 isozyme (SRD5A2) has been determined. 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, and phenotypic severity was compared with previously published data. The p.R227Q variant, which belongs to the NADPH-binding residue mutation category, exhibited a more masculine phenotype (higher external masculinization 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, the variants categorized as structure-destabilizing and small to bulky residue mutations showed moderate to severe phenotypes, and those categorized 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. Furthermore, the categorization of SRD5A2 gene variants according to the SRD5A2 structure facilitates the prediction of the severity of 5αRD2 and the management and genetic counseling of patients affected by it.
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spelling pubmed-99664102023-02-26 The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective Seo, Jieun Shin, Saeam Kim, Sang-woon Kim, Su Jin Lee, Myeongseob Song, Kyungchul Suh, Junghwan Lee, Seung-Tae Lee, Yong Seung Chae, Hyun Wook Kim, Ho-Seong Choi, Jong Rak Han, Sangwon Kwon, Ahreum Int J Mol Sci Article The phenotype of the 5α-reductase type 2 deficiency (5αRD2) by the SRD5A2 gene mutation varies, and although there have been many attempts, the genotype-phenotype correlation still has not yet been adequately evaluated. Recently, the crystal structure of the 5α-reductase type 2 isozyme (SRD5A2) has been determined. 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, and phenotypic severity was compared with previously published data. The p.R227Q variant, which belongs to the NADPH-binding residue mutation category, exhibited a more masculine phenotype (higher external masculinization 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, the variants categorized as structure-destabilizing and small to bulky residue mutations showed moderate to severe phenotypes, and those categorized 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. Furthermore, the categorization of SRD5A2 gene variants according to the SRD5A2 structure facilitates the prediction of the severity of 5αRD2 and the management and genetic counseling of patients affected by it. MDPI 2023-02-07 /pmc/articles/PMC9966410/ /pubmed/36834714 http://dx.doi.org/10.3390/ijms24043297 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seo, Jieun
Shin, Saeam
Kim, Sang-woon
Kim, Su Jin
Lee, Myeongseob
Song, Kyungchul
Suh, Junghwan
Lee, Seung-Tae
Lee, Yong Seung
Chae, Hyun Wook
Kim, Ho-Seong
Choi, Jong Rak
Han, Sangwon
Kwon, Ahreum
The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective
title The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective
title_full The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective
title_fullStr The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective
title_full_unstemmed The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective
title_short The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective
title_sort genotype-phenotype correlation in human 5α-reductase type 2 deficiency: classified and analyzed from a srd5a2 structural perspective
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966410/
https://www.ncbi.nlm.nih.gov/pubmed/36834714
http://dx.doi.org/10.3390/ijms24043297
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