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
Affiliations
Haifaou Younoussa
Cell Environment DNA Damage R&D, Genopole, 91000 Evry-Courcouronnes, France
Macoura Gadji
Service of Biological Hematology & Oncology-Hematology (BHOH), National Centre of Blood Transfusion (NCBT), Faculty of Medicine, Pharmacy and Odonto-Stomatology (FMPO), Cheikh Anta Diop University of Dakar (UCAD), Dakar BP 5002, Senegal
Mamadou Soumboundou
Medical Diagnostic Laboratory, Diamniadjo Hospital, UFR-Santé de Thiès, Iba Der Thiam University of Thies, Thiès BP A967, Senegal
Bruno Colicchio
IRIMAS, Institut de Recherche en Informatique, Mathématiques, Automatique et Signal, Université de Haute-Alsace, 68093 Mulhouse, France
Ahmed Said
Cell Environment DNA Damage R&D, Genopole, 91000 Evry-Courcouronnes, France
Ndeye Aby Ndoye
Service de Chirurgie Pédiatrique de L’hôpital Albert Royer, Cheikh Anta Diop Ave, Dakar BP 25755, Senegal
Steffen Junker
Institute of Biomedicine, University of Aarhus, DK-8000 Aarhus, Denmark
Andreas Plesch
MetaSystems GmbH, D-68804 Altlussheim, Germany
Leonhard Heidingsfelder
MetaSystems GmbH, D-68804 Altlussheim, Germany
Ndeye Rama Diagne
Medical Diagnostic Laboratory, Diamniadjo Hospital, UFR-Santé de Thiès, Iba Der Thiam University of Thies, Thiès BP A967, Senegal
Alain Dieterlen
IRIMAS, Institut de Recherche en Informatique, Mathématiques, Automatique et Signal, Université de Haute-Alsace, 68093 Mulhouse, France
Philippe Voisin
Cell Environment DNA Damage R&D, Genopole, 91000 Evry-Courcouronnes, France
Patrice Carde
Department of Hematology, Gustave Roussy Cancer Campus, 94805 Villejuif, France
Eric Jeandidier
Service de Génétique, Groupe Hospitalier de la Région de Mulhouse Sud-Alsace, 68100 Mulhouse, France
Radhia M’kacher
Cell Environment DNA Damage R&D, Genopole, 91000 Evry-Courcouronnes, France
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.
