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Disorders of sex development: Genetic characterization of a patient cohort
Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anato...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896350/ https://www.ncbi.nlm.nih.gov/pubmed/31746433 http://dx.doi.org/10.3892/mmr.2019.10819 |
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author | García-Acero, Mary Moreno-Niño, Olga Suárez-Obando, Fernando Molina, Mónica Manotas, María Carolina Prieto, Juan Carlos Forero, Catalina Céspedes, Camila Pérez, Jaime Fernandez, Nicolas Rojas, Adriana |
author_facet | García-Acero, Mary Moreno-Niño, Olga Suárez-Obando, Fernando Molina, Mónica Manotas, María Carolina Prieto, Juan Carlos Forero, Catalina Céspedes, Camila Pérez, Jaime Fernandez, Nicolas Rojas, Adriana |
author_sort | García-Acero, Mary |
collection | PubMed |
description | Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as ‘other’ since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad-spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations. |
format | Online Article Text |
id | pubmed-6896350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-68963502019-12-09 Disorders of sex development: Genetic characterization of a patient cohort García-Acero, Mary Moreno-Niño, Olga Suárez-Obando, Fernando Molina, Mónica Manotas, María Carolina Prieto, Juan Carlos Forero, Catalina Céspedes, Camila Pérez, Jaime Fernandez, Nicolas Rojas, Adriana Mol Med Rep Articles Disorders of sex development (DSDs) are congenital conditions in which the external appearance of the individual does not coincide with the chromosomal constitution or the gonadal sex. In other words, there is an ambiguous or intermediate condition between the male and female phenotypes of the anatomical sex. These atypical conditions are manifested in several ways, ranging from genital ambiguity to phenotypes that are so attenuated that they can go unnoticed or appear normal. Currently, there is a lack of understanding of the factors responsible for these outcomes; however, they are likely to be conditioned by genetic, hormonal and environmental factors during prenatal and postnatal development. The present study determined the genetic etiology of DSDs in Colombian patients by conventional cytogenetic analysis, FISH and MLPA (for SF1, DAX1, SOX9, SRY and WNT4). A cohort of 43 patients with clinical phenotypes of sex development disorder was used in the present study. Using this multistep experimental approach, a diagnostic percentage of 25.58% was obtained: 17 patients (39.53%) were classified as having gonadal development disorders, the majority of which were ovotesticular disorders with numerical and/or structural alterations of the sex chromosomes, 9 patients (20.93%) were classified as having testicular DSD with a 46,XY karyotype, and 3 patients (6.98%) as having ovarian DSD with a 46,XX karyotype. The remaining 14 patients (32.56%) were classified as ‘other’ since they could not be grouped into a specific class of gonadal development, corresponding to hypospadias and multiple congenital anomalies. These findings highlight the importance of histological and cytogenetic studies in a gonadal biopsy. In 11/43 cases, the multistep experimental protocol presented in the present study yielded etiological or histological findings that could be used to define the medical management of patients with DSDs. In conclusion, for the etiological diagnosis of DSDs, a broad-spectrum approach that includes endocrinological tests, conventional karyotyping, molecular karyotyping by FISH and, molecular tests is required, in addition to gonadal tissue analyses, to identify genetic alterations. D.A. Spandidos 2020-01 2019-11-12 /pmc/articles/PMC6896350/ /pubmed/31746433 http://dx.doi.org/10.3892/mmr.2019.10819 Text en Copyright: © García-Acero et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles García-Acero, Mary Moreno-Niño, Olga Suárez-Obando, Fernando Molina, Mónica Manotas, María Carolina Prieto, Juan Carlos Forero, Catalina Céspedes, Camila Pérez, Jaime Fernandez, Nicolas Rojas, Adriana Disorders of sex development: Genetic characterization of a patient cohort |
title | Disorders of sex development: Genetic characterization of a patient cohort |
title_full | Disorders of sex development: Genetic characterization of a patient cohort |
title_fullStr | Disorders of sex development: Genetic characterization of a patient cohort |
title_full_unstemmed | Disorders of sex development: Genetic characterization of a patient cohort |
title_short | Disorders of sex development: Genetic characterization of a patient cohort |
title_sort | disorders of sex development: genetic characterization of a patient cohort |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896350/ https://www.ncbi.nlm.nih.gov/pubmed/31746433 http://dx.doi.org/10.3892/mmr.2019.10819 |
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