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Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies

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Harvard

Portnoi, M-F, Dumargne, M-C, Rojo, S, Witchel, SF, Duncan, AJ, Eozenou, C, Bignon-Topalovic, J, Yatsenko, SA, Rajkovic, A, Reyes-Mugica, M, Almstrup, K, Fusee, L, Srivastava, Y, Chantot-Bastaraud, S, Hyon, C, Louis-Sylvestre, C, Validire, P, de Malleray Pichard, C, Ravel, C, Christin-Maitre, S, Brauner, R, Rossetti, R, Persani, L, Charreau, EH, Dain, L, Chiauzzi, VA, Mazen, I, Rouba, H, Schluth-Bolard, C, MacGowan, S, McLean, WHI, Patin, E, Rajpert-De Meyts, E, Jauch, R, Achermann, JC, Siffroi, J-P, McElreavey, K & Bashamboo, A 2018, 'Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies' Human Molecular Genetics, vol. 27, no. 7, pp. 1228-1240. https://doi.org/10.1093/hmg/ddy037

APA

Portnoi, M-F., Dumargne, M-C., Rojo, S., Witchel, S. F., Duncan, A. J., Eozenou, C., ... Bashamboo, A. (2018). Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies. Human Molecular Genetics, 27(7), 1228-1240. https://doi.org/10.1093/hmg/ddy037

CBE

Portnoi M-F, Dumargne M-C, Rojo S, Witchel SF, Duncan AJ, Eozenou C, Bignon-Topalovic J, Yatsenko SA, Rajkovic A, Reyes-Mugica M, Almstrup K, Fusee L, Srivastava Y, Chantot-Bastaraud S, Hyon C, Louis-Sylvestre C, Validire P, de Malleray Pichard C, Ravel C, Christin-Maitre S, Brauner R, Rossetti R, Persani L, Charreau EH, Dain L, Chiauzzi VA, Mazen I, Rouba H, Schluth-Bolard C, MacGowan S, McLean WHI, Patin E, Rajpert-De Meyts E, Jauch R, Achermann JC, Siffroi J-P, McElreavey K, Bashamboo A. 2018. Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies. Human Molecular Genetics. 27(7):1228-1240. https://doi.org/10.1093/hmg/ddy037

MLA

Vancouver

Author

Portnoi, Marie-France ; Dumargne, Marie-Charlotte ; Rojo, Sandra ; Witchel, Selma F ; Duncan, Andrew J ; Eozenou, Caroline ; Bignon-Topalovic, Joelle ; Yatsenko, Svetlana A ; Rajkovic, Aleksandar ; Reyes-Mugica, Miguel ; Almstrup, Kristian ; Fusee, Leila ; Srivastava, Yogesh ; Chantot-Bastaraud, Sandra ; Hyon, Capucine ; Louis-Sylvestre, Christine ; Validire, Pierre ; de Malleray Pichard, Caroline ; Ravel, Celia ; Christin-Maitre, Sophie ; Brauner, Raja ; Rossetti, Raffaella ; Persani, Luca ; Charreau, Eduardo H ; Dain, Liliana ; Chiauzzi, Violeta A ; Mazen, Inas ; Rouba, Hassan ; Schluth-Bolard, Caroline ; MacGowan, Stuart ; McLean, W H Irwin ; Patin, Etienne ; Rajpert-De Meyts, Ewa ; Jauch, Ralf ; Achermann, John C ; Siffroi, Jean-Pierre ; McElreavey, Ken ; Bashamboo, Anu. / Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies. In: Human Molecular Genetics. 2018 ; Vol. 27, No. 7. pp. 1228-1240.

Bibtex

@article{2adad36c3e1441aeae59b5fef7b59595,
title = "Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies",
abstract = "SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5{\%}; P < 0.05) and POI (5.06{\%}; P = 4.5 × 10-5) as compared with fertile/normospermic control populations (0.74{\%}). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.",
keywords = "46, XX Disorders of Sex Development/genetics, Adolescent, Child, Disorder of Sex Development, 46,XY/genetics, Female, Humans, Male, Mutation, Missense, Oligospermia/genetics, Primary Ovarian Insufficiency/genetics, SOXE Transcription Factors/genetics",
author = "Marie-France Portnoi and Marie-Charlotte Dumargne and Sandra Rojo and Witchel, {Selma F} and Duncan, {Andrew J} and Caroline Eozenou and Joelle Bignon-Topalovic and Yatsenko, {Svetlana A} and Aleksandar Rajkovic and Miguel Reyes-Mugica and Kristian Almstrup and Leila Fusee and Yogesh Srivastava and Sandra Chantot-Bastaraud and Capucine Hyon and Christine Louis-Sylvestre and Pierre Validire and {de Malleray Pichard}, Caroline and Celia Ravel and Sophie Christin-Maitre and Raja Brauner and Raffaella Rossetti and Luca Persani and Charreau, {Eduardo H} and Liliana Dain and Chiauzzi, {Violeta A} and Inas Mazen and Hassan Rouba and Caroline Schluth-Bolard and Stuart MacGowan and McLean, {W H Irwin} and Etienne Patin and {Rajpert-De Meyts}, Ewa and Ralf Jauch and Achermann, {John C} and Jean-Pierre Siffroi and Ken McElreavey and Anu Bashamboo",
year = "2018",
month = "4",
day = "1",
doi = "10.1093/hmg/ddy037",
language = "English",
volume = "27",
pages = "1228--1240",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "7",

}

RIS

TY - JOUR

T1 - Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies

AU - Portnoi, Marie-France

AU - Dumargne, Marie-Charlotte

AU - Rojo, Sandra

AU - Witchel, Selma F

AU - Duncan, Andrew J

AU - Eozenou, Caroline

AU - Bignon-Topalovic, Joelle

AU - Yatsenko, Svetlana A

AU - Rajkovic, Aleksandar

AU - Reyes-Mugica, Miguel

AU - Almstrup, Kristian

AU - Fusee, Leila

AU - Srivastava, Yogesh

AU - Chantot-Bastaraud, Sandra

AU - Hyon, Capucine

AU - Louis-Sylvestre, Christine

AU - Validire, Pierre

AU - de Malleray Pichard, Caroline

AU - Ravel, Celia

AU - Christin-Maitre, Sophie

AU - Brauner, Raja

AU - Rossetti, Raffaella

AU - Persani, Luca

AU - Charreau, Eduardo H

AU - Dain, Liliana

AU - Chiauzzi, Violeta A

AU - Mazen, Inas

AU - Rouba, Hassan

AU - Schluth-Bolard, Caroline

AU - MacGowan, Stuart

AU - McLean, W H Irwin

AU - Patin, Etienne

AU - Rajpert-De Meyts, Ewa

AU - Jauch, Ralf

AU - Achermann, John C

AU - Siffroi, Jean-Pierre

AU - McElreavey, Ken

AU - Bashamboo, Anu

PY - 2018/4/1

Y1 - 2018/4/1

N2 - SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P = 4.5 × 10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.

AB - SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P = 4.5 × 10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.

KW - 46, XX Disorders of Sex Development/genetics

KW - Adolescent

KW - Child

KW - Disorder of Sex Development, 46,XY/genetics

KW - Female

KW - Humans

KW - Male

KW - Mutation, Missense

KW - Oligospermia/genetics

KW - Primary Ovarian Insufficiency/genetics

KW - SOXE Transcription Factors/genetics

U2 - 10.1093/hmg/ddy037

DO - 10.1093/hmg/ddy037

M3 - Journal article

VL - 27

SP - 1228

EP - 1240

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 7

ER -

ID: 56448817