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

Area of Science:

• Genetics and Molecular Biology
• Developmental Biology
• Human Genetics

Background:

• Disorders of Sex Development (DSDs) are complex conditions affecting sexual development, with increasing incidence in sub-Saharan Africa.
• The underlying causes and mechanisms of DSDs remain poorly understood, necessitating further investigation.
• Telomere dysfunction has emerged as a potential factor in various genetic disorders.

Purpose of the Study:

• To investigate the cytogenetic profiles of Disorders of Sex Development (DSD) patients in Senegal.
• To explore the potential role of telomere dysfunction in the etiology of DSDs.
• To establish a correlation between telomere length, telomere aberrations, and chromosomal abnormalities in DSD patients.

Main Methods:

• Retrospective analysis of peripheral blood lymphocytes from 35 DSD patients and 150 healthy controls.
• Conventional cytogenetics, telomere, and centromere staining.
• Multiplex fluorescence in situ hybridization (FISH) with SRY-specific probes.

Main Results:

• Cytogenetic analysis revealed normal karyotypes in most patients, but identified structural chromosome aberrations in 22%.
• DSD patients exhibited significantly reduced mean telomere lengths compared to healthy controls.
• Telomere analysis indicated an increased rate of telomere aberrations, including telomere loss and doublets, in DSD patients.

Conclusions:

• This study provides the first evidence correlating telomere dysfunction with Disorders of Sex Development (DSDs).
• Telomere dysfunction may be linked to DSD pathogenesis through mechanisms like DNA repair deficiencies or specific gene mutations.
• Telomere analysis is recommended for prenatal diagnostics and the evaluation of diagnosed genetic DSD disorders.