Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development

Haifaou Younoussa; Macoura Gadji; Mamadou Soumboundou; Bruno Colicchio; Ahmed Said; Ndeye Aby Ndoye; Steffen Junker; Andreas Plesch; Leonhard Heidingsfelder; Ndeye Rama Diagne; Alain Dieterlen; Philippe Voisin; Patrice Carde; Eric Jeandidier; Radhia M’kacher

doi:10.3390/biomedicines12030565

Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development

Haifaou Younoussa, Macoura Gadji^*, Mamadou Soumboundou, Bruno Colicchio, Ahmed Said, Ndeye Aby Ndoye, Steffen Junker, Andreas Plesch, Leonhard Heidingsfelder, Ndeye Rama Diagne, Alain Dieterlen, Philippe Voisin, Patrice Carde, Eric Jeandidier, Radhia M’kacher^*

^*Corresponding author for this work

Department of Biomedicine - Forskning og uddannelse, Vest

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients. Materials and methods: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0–18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed. Results: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations. Conclusions: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders.

Original language	English
Article number	565
Journal	Biomedicines
Volume	12
Issue	3
ISSN	2227-9059
DOIs	https://doi.org/10.3390/biomedicines12030565
Publication status	Published - Mar 2024

Keywords

chromosomal aberrations
DSDs
telomere dysfunctions
telomere shortening

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10.3390/biomedicines12030565Licence: CC BY

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Younoussa, H., Gadji, M., Soumboundou, M., Colicchio, B., Said, A., Ndoye, N. A., Junker, S., Plesch, A., Heidingsfelder, L., Diagne, N. R., Dieterlen, A., Voisin, P., Carde, P., Jeandidier, E., & M’kacher, R. (2024). Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development. Biomedicines, 12(3), Article 565. https://doi.org/10.3390/biomedicines12030565

@article{20c31e43ff42462caef039de70d0dd14,

title = "Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development",

abstract = "Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients. Materials and methods: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0–18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed. Results: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations. Conclusions: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders.",

keywords = "chromosomal aberrations, DSDs, telomere dysfunctions, telomere shortening",

author = "Haifaou Younoussa and Macoura Gadji and Mamadou Soumboundou and Bruno Colicchio and Ahmed Said and Ndoye, {Ndeye Aby} and Steffen Junker and Andreas Plesch and Leonhard Heidingsfelder and Diagne, {Ndeye Rama} and Alain Dieterlen and Philippe Voisin and Patrice Carde and Eric Jeandidier and Radhia M{\textquoteright}kacher",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

month = mar,

doi = "10.3390/biomedicines12030565",

language = "English",

volume = "12",

journal = "Biomedicines",

issn = "2227-9059",

publisher = "MDPI",

number = "3",

}

Younoussa, H, Gadji, M, Soumboundou, M, Colicchio, B, Said, A, Ndoye, NA, Junker, S, Plesch, A, Heidingsfelder, L, Diagne, NR, Dieterlen, A, Voisin, P, Carde, P, Jeandidier, E & M’kacher, R 2024, 'Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development', Biomedicines, vol. 12, no. 3, 565. https://doi.org/10.3390/biomedicines12030565

TY - JOUR

T1 - Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development

AU - Younoussa, Haifaou

AU - Gadji, Macoura

AU - Soumboundou, Mamadou

AU - Colicchio, Bruno

AU - Said, Ahmed

AU - Ndoye, Ndeye Aby

AU - Junker, Steffen

AU - Plesch, Andreas

AU - Heidingsfelder, Leonhard

AU - Diagne, Ndeye Rama

AU - Dieterlen, Alain

AU - Voisin, Philippe

AU - Carde, Patrice

AU - Jeandidier, Eric

AU - M’kacher, Radhia

PY - 2024/3

Y1 - 2024/3

N2 - Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients. Materials and methods: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0–18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed. Results: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations. Conclusions: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders.

AB - Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients. Materials and methods: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0–18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed. Results: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations. Conclusions: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders.

KW - chromosomal aberrations

KW - DSDs

KW - telomere dysfunctions

KW - telomere shortening

U2 - 10.3390/biomedicines12030565

DO - 10.3390/biomedicines12030565

M3 - Journal article

C2 - 38540177

AN - SCOPUS:85188731040

SN - 2227-9059

VL - 12

JO - Biomedicines

JF - Biomedicines

IS - 3

M1 - 565

ER -

Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development

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Keywords

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