Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development

Fatou Diop Gueye; Arame Ndiaye; Mame Venus Gueye; Ndiaga Diop; Adji Dieynaba Diallo; Rokhaya Ndiaye; Oumar Faye; Mama Sy Diallo

doi:doi:10.11648/j.ijgg.20231103.12

Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development

Fatou Diop Gueye, Arame Ndiaye, Mame Venus Gueye, Ndiaga Diop, Adji Dieynaba Diallo, Rokhaya Ndiaye, Oumar Faye, Mama Sy Diallo

Published in International Journal of Genetics and Genomics (Volume 11, Issue 3)

Received: 31 May 2023 Accepted: 21 June 2023 Published: 6 July 2023

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Abstract

The genes SRY, SOX9 and DAX1, key genes in human sex determination, due to their associated sex-reversal phenotypes (Figure 1) upon mutation (SRY, SOX9) or overexpression (SOX9, DAX1). The objective of this study was to characterize mutations occurring in SRY, DAX1 and SOX9 genes known to be implicated in the sexual determinism to better understand disorders of sex development (DSD) in our population. 87 DSD patients were identified and for which we carried out a clinical review and karyotype. Moreover, molecular analysis of the SRY, SOX9, and DAX1 genes (PCR amplification, Sanger sequencing and expression by qPCR) have been done. Based on the results, it was found in patients 46, XX an absence of female internal genitals or the presence of testicles depending on the patients while for patients 46, XY no testicles were found. Among the 87 patients, the genomic DNA of 29 of them was extracted and used for molecular analysis, which identified 4 patients 46, XX SRY positive and 2 patients 46, XY SRY negative. In addition, the sequencing of the SRY, SOX9 and DAX1 genes revealed different mutations, including two new for SRY (c.265 G>A, p.89Glu>Lys in 2 patients 46, XY and c.171 G>C, p.57Gln>His in a patient 46, XX) and one variant (c.349 G>C, p.117Gln>Glu) in coding sequence for SOX9 in a 46, XY SRY positive patient while for DAX1, any new mutation was found. These results highlight the differences in the expression of the SRY, SOX9 and DAX1 genes in the determination of sex in humans and increase the spectrum of mutations of genes in cascade. The complexity of gene interactions that lead to the development of the bipotential gonad to a testicle or ovary is increasingly recognized, but there is still much to be done.

Published in	International Journal of Genetics and Genomics (Volume 11, Issue 3)
DOI	10.11648/j.ijgg.20231103.12
Page(s)	71-80
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

DSD, AHC, SRY, DAX1, SOX9

References

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Fatou Diop Gueye, Arame Ndiaye, Mame Venus Gueye, Ndiaga Diop, Adji Dieynaba Diallo, et al. (2023). Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development. International Journal of Genetics and Genomics, 11(3), 71-80. https://doi.org/10.11648/j.ijgg.20231103.12

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Fatou Diop Gueye; Arame Ndiaye; Mame Venus Gueye; Ndiaga Diop; Adji Dieynaba Diallo, et al. Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development. Int. J. Genet. Genomics 2023, 11(3), 71-80. doi: 10.11648/j.ijgg.20231103.12

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Fatou Diop Gueye, Arame Ndiaye, Mame Venus Gueye, Ndiaga Diop, Adji Dieynaba Diallo, et al. Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development. Int J Genet Genomics. 2023;11(3):71-80. doi: 10.11648/j.ijgg.20231103.12

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@article{10.11648/j.ijgg.20231103.12,
  author = {Fatou Diop Gueye and Arame Ndiaye and Mame Venus Gueye and Ndiaga Diop and Adji Dieynaba Diallo and Rokhaya Ndiaye and Oumar Faye and Mama Sy Diallo},
  title = {Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development},
  journal = {International Journal of Genetics and Genomics},
  volume = {11},
  number = {3},
  pages = {71-80},
  doi = {10.11648/j.ijgg.20231103.12},
  url = {https://doi.org/10.11648/j.ijgg.20231103.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20231103.12},
  abstract = {The genes SRY, SOX9 and DAX1, key genes in human sex determination, due to their associated sex-reversal phenotypes (Figure 1) upon mutation (SRY, SOX9) or overexpression (SOX9, DAX1). The objective of this study was to characterize mutations occurring in SRY, DAX1 and SOX9 genes known to be implicated in the sexual determinism to better understand disorders of sex development (DSD) in our population. 87 DSD patients were identified and for which we carried out a clinical review and karyotype. Moreover, molecular analysis of the SRY, SOX9, and DAX1 genes (PCR amplification, Sanger sequencing and expression by qPCR) have been done. Based on the results, it was found in patients 46, XX an absence of female internal genitals or the presence of testicles depending on the patients while for patients 46, XY no testicles were found. Among the 87 patients, the genomic DNA of 29 of them was extracted and used for molecular analysis, which identified 4 patients 46, XX SRY positive and 2 patients 46, XY SRY negative. In addition, the sequencing of the SRY, SOX9 and DAX1 genes revealed different mutations, including two new for SRY (c.265 G>A, p.89Glu>Lys in 2 patients 46, XY and c.171 G>C, p.57Gln>His in a patient 46, XX) and one variant (c.349 G>C, p.117Gln>Glu) in coding sequence for SOX9 in a 46, XY SRY positive patient while for DAX1, any new mutation was found. These results highlight the differences in the expression of the SRY, SOX9 and DAX1 genes in the determination of sex in humans and increase the spectrum of mutations of genes in cascade. The complexity of gene interactions that lead to the development of the bipotential gonad to a testicle or ovary is increasingly recognized, but there is still much to be done.},
 year = {2023}
}

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TY  - JOUR
T1  - Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development
AU  - Fatou Diop Gueye
AU  - Arame Ndiaye
AU  - Mame Venus Gueye
AU  - Ndiaga Diop
AU  - Adji Dieynaba Diallo
AU  - Rokhaya Ndiaye
AU  - Oumar Faye
AU  - Mama Sy Diallo
Y1  - 2023/07/06
PY  - 2023
N1  - https://doi.org/10.11648/j.ijgg.20231103.12
DO  - 10.11648/j.ijgg.20231103.12
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 71
EP  - 80
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20231103.12
AB  - The genes SRY, SOX9 and DAX1, key genes in human sex determination, due to their associated sex-reversal phenotypes (Figure 1) upon mutation (SRY, SOX9) or overexpression (SOX9, DAX1). The objective of this study was to characterize mutations occurring in SRY, DAX1 and SOX9 genes known to be implicated in the sexual determinism to better understand disorders of sex development (DSD) in our population. 87 DSD patients were identified and for which we carried out a clinical review and karyotype. Moreover, molecular analysis of the SRY, SOX9, and DAX1 genes (PCR amplification, Sanger sequencing and expression by qPCR) have been done. Based on the results, it was found in patients 46, XX an absence of female internal genitals or the presence of testicles depending on the patients while for patients 46, XY no testicles were found. Among the 87 patients, the genomic DNA of 29 of them was extracted and used for molecular analysis, which identified 4 patients 46, XX SRY positive and 2 patients 46, XY SRY negative. In addition, the sequencing of the SRY, SOX9 and DAX1 genes revealed different mutations, including two new for SRY (c.265 G>A, p.89Glu>Lys in 2 patients 46, XY and c.171 G>C, p.57Gln>His in a patient 46, XX) and one variant (c.349 G>C, p.117Gln>Glu) in coding sequence for SOX9 in a 46, XY SRY positive patient while for DAX1, any new mutation was found. These results highlight the differences in the expression of the SRY, SOX9 and DAX1 genes in the determination of sex in humans and increase the spectrum of mutations of genes in cascade. The complexity of gene interactions that lead to the development of the bipotential gonad to a testicle or ovary is increasingly recognized, but there is still much to be done.
VL  - 11
IS  - 3
ER  -

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Fatou Diop Gueye

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Arame Ndiaye

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Mame Venus Gueye

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Ndiaga Diop

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Adji Dieynaba Diallo

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Rokhaya Ndiaye

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Oumar Faye

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal
Mama Sy Diallo

Laboratory of Clinical Cytology-Cytogenetic-Biology of Reproduction and Human Development, Cytogenetic Unit, Aristide Le Dantec Hospital, Dakar, Senegal

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Fatou Diop Gueye, Arame Ndiaye, Mame Venus Gueye, Ndiaga Diop, Adji Dieynaba Diallo, et al. (2023). Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development. International Journal of Genetics and Genomics, 11(3), 71-80. https://doi.org/10.11648/j.ijgg.20231103.12

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Fatou Diop Gueye; Arame Ndiaye; Mame Venus Gueye; Ndiaga Diop; Adji Dieynaba Diallo, et al. Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development. Int. J. Genet. Genomics 2023, 11(3), 71-80. doi: 10.11648/j.ijgg.20231103.12

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AMA Style

Fatou Diop Gueye, Arame Ndiaye, Mame Venus Gueye, Ndiaga Diop, Adji Dieynaba Diallo, et al. Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development. Int J Genet Genomics. 2023;11(3):71-80. doi: 10.11648/j.ijgg.20231103.12

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@article{10.11648/j.ijgg.20231103.12,
  author = {Fatou Diop Gueye and Arame Ndiaye and Mame Venus Gueye and Ndiaga Diop and Adji Dieynaba Diallo and Rokhaya Ndiaye and Oumar Faye and Mama Sy Diallo},
  title = {Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development},
  journal = {International Journal of Genetics and Genomics},
  volume = {11},
  number = {3},
  pages = {71-80},
  doi = {10.11648/j.ijgg.20231103.12},
  url = {https://doi.org/10.11648/j.ijgg.20231103.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20231103.12},
  abstract = {The genes SRY, SOX9 and DAX1, key genes in human sex determination, due to their associated sex-reversal phenotypes (Figure 1) upon mutation (SRY, SOX9) or overexpression (SOX9, DAX1). The objective of this study was to characterize mutations occurring in SRY, DAX1 and SOX9 genes known to be implicated in the sexual determinism to better understand disorders of sex development (DSD) in our population. 87 DSD patients were identified and for which we carried out a clinical review and karyotype. Moreover, molecular analysis of the SRY, SOX9, and DAX1 genes (PCR amplification, Sanger sequencing and expression by qPCR) have been done. Based on the results, it was found in patients 46, XX an absence of female internal genitals or the presence of testicles depending on the patients while for patients 46, XY no testicles were found. Among the 87 patients, the genomic DNA of 29 of them was extracted and used for molecular analysis, which identified 4 patients 46, XX SRY positive and 2 patients 46, XY SRY negative. In addition, the sequencing of the SRY, SOX9 and DAX1 genes revealed different mutations, including two new for SRY (c.265 G>A, p.89Glu>Lys in 2 patients 46, XY and c.171 G>C, p.57Gln>His in a patient 46, XX) and one variant (c.349 G>C, p.117Gln>Glu) in coding sequence for SOX9 in a 46, XY SRY positive patient while for DAX1, any new mutation was found. These results highlight the differences in the expression of the SRY, SOX9 and DAX1 genes in the determination of sex in humans and increase the spectrum of mutations of genes in cascade. The complexity of gene interactions that lead to the development of the bipotential gonad to a testicle or ovary is increasingly recognized, but there is still much to be done.},
 year = {2023}
}

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TY  - JOUR
T1  - Mutation Profile of SOX9, DAX1, and SRY Genes in Senegalese Patients with Disorders of Sex Development
AU  - Fatou Diop Gueye
AU  - Arame Ndiaye
AU  - Mame Venus Gueye
AU  - Ndiaga Diop
AU  - Adji Dieynaba Diallo
AU  - Rokhaya Ndiaye
AU  - Oumar Faye
AU  - Mama Sy Diallo
Y1  - 2023/07/06
PY  - 2023
N1  - https://doi.org/10.11648/j.ijgg.20231103.12
DO  - 10.11648/j.ijgg.20231103.12
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 71
EP  - 80
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20231103.12
AB  - The genes SRY, SOX9 and DAX1, key genes in human sex determination, due to their associated sex-reversal phenotypes (Figure 1) upon mutation (SRY, SOX9) or overexpression (SOX9, DAX1). The objective of this study was to characterize mutations occurring in SRY, DAX1 and SOX9 genes known to be implicated in the sexual determinism to better understand disorders of sex development (DSD) in our population. 87 DSD patients were identified and for which we carried out a clinical review and karyotype. Moreover, molecular analysis of the SRY, SOX9, and DAX1 genes (PCR amplification, Sanger sequencing and expression by qPCR) have been done. Based on the results, it was found in patients 46, XX an absence of female internal genitals or the presence of testicles depending on the patients while for patients 46, XY no testicles were found. Among the 87 patients, the genomic DNA of 29 of them was extracted and used for molecular analysis, which identified 4 patients 46, XX SRY positive and 2 patients 46, XY SRY negative. In addition, the sequencing of the SRY, SOX9 and DAX1 genes revealed different mutations, including two new for SRY (c.265 G>A, p.89Glu>Lys in 2 patients 46, XY and c.171 G>C, p.57Gln>His in a patient 46, XX) and one variant (c.349 G>C, p.117Gln>Glu) in coding sequence for SOX9 in a 46, XY SRY positive patient while for DAX1, any new mutation was found. These results highlight the differences in the expression of the SRY, SOX9 and DAX1 genes in the determination of sex in humans and increase the spectrum of mutations of genes in cascade. The complexity of gene interactions that lead to the development of the bipotential gonad to a testicle or ovary is increasingly recognized, but there is still much to be done.
VL  - 11
IS  - 3
ER  -

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