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Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development
Background: The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the SRD5A2 gene, which encodes this enzyme, are responsible for 46,XY DSD. Objective: The objective of the study was to investigate the genetic etiology of 46,XY...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829113/ https://www.ncbi.nlm.nih.gov/pubmed/35154247 http://dx.doi.org/10.3389/fgene.2021.794476 |
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author | María Guadalupe, Ortiz-López Katy, Sánchez-Pozos Charmina, Aguirre-Alvarado Vihko, Pirkko Marta, Menjivar |
author_facet | María Guadalupe, Ortiz-López Katy, Sánchez-Pozos Charmina, Aguirre-Alvarado Vihko, Pirkko Marta, Menjivar |
author_sort | María Guadalupe, Ortiz-López |
collection | PubMed |
description | Background: The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the SRD5A2 gene, which encodes this enzyme, are responsible for 46,XY DSD. Objective: The objective of the study was to investigate the genetic etiology of 46,XY DSD in two Mexican families with affected children. Materials and methods: The SRD5A2 gene of the parents and affected children was screened in both families via polymerase chain reaction amplification and DNA direct sequencing. The role of genetic variants in enzymatic activity was tested by site-directed mutagenesis. Results: Subject 1 presented two variants: p.Glu197Asp and p.Pro212Arg. Subject 2 was homozygous for the variant p.Glu197Asp. The two variants were reported in early studies. The directed mutagenesis study showed that the p.Glu197Asp and p.Pro212Arg variants lead to a total loss of enzymatic activity and, consequently, abnormal genitalia development in the patients. Conclusion: These results suggest that p.Glu197Asp and p.Pro212Arg are pathogenic variants that lead to the phenotypic expression of DSD. 5α-RD2 is of extreme importance not only because of its frequency (it is rare) but also because of its significance in understanding the mechanism of androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior. |
format | Online Article Text |
id | pubmed-8829113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88291132022-02-11 Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development María Guadalupe, Ortiz-López Katy, Sánchez-Pozos Charmina, Aguirre-Alvarado Vihko, Pirkko Marta, Menjivar Front Genet Genetics Background: The 5α-reductase type 2 deficiency (5α-RD2) is a specific form of disorder of sexual development (DSD). Pathogenic variants in the SRD5A2 gene, which encodes this enzyme, are responsible for 46,XY DSD. Objective: The objective of the study was to investigate the genetic etiology of 46,XY DSD in two Mexican families with affected children. Materials and methods: The SRD5A2 gene of the parents and affected children was screened in both families via polymerase chain reaction amplification and DNA direct sequencing. The role of genetic variants in enzymatic activity was tested by site-directed mutagenesis. Results: Subject 1 presented two variants: p.Glu197Asp and p.Pro212Arg. Subject 2 was homozygous for the variant p.Glu197Asp. The two variants were reported in early studies. The directed mutagenesis study showed that the p.Glu197Asp and p.Pro212Arg variants lead to a total loss of enzymatic activity and, consequently, abnormal genitalia development in the patients. Conclusion: These results suggest that p.Glu197Asp and p.Pro212Arg are pathogenic variants that lead to the phenotypic expression of DSD. 5α-RD2 is of extreme importance not only because of its frequency (it is rare) but also because of its significance in understanding the mechanism of androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior. Frontiers Media S.A. 2022-01-27 /pmc/articles/PMC8829113/ /pubmed/35154247 http://dx.doi.org/10.3389/fgene.2021.794476 Text en Copyright © 2022 María Guadalupe, Katy, Charmina, Vihko and Marta. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics María Guadalupe, Ortiz-López Katy, Sánchez-Pozos Charmina, Aguirre-Alvarado Vihko, Pirkko Marta, Menjivar Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development |
title | Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development |
title_full | Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development |
title_fullStr | Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development |
title_full_unstemmed | Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development |
title_short | Molecular Characterization of Two Known SRD5A2 Gene Variants in Mexican Patients With Disorder of Sexual Development |
title_sort | molecular characterization of two known srd5a2 gene variants in mexican patients with disorder of sexual development |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8829113/ https://www.ncbi.nlm.nih.gov/pubmed/35154247 http://dx.doi.org/10.3389/fgene.2021.794476 |
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