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.
ABSTRACT
OBJECTIVES: To describe prevalence and risk factors for wasting and stunting among HIV-infected children with a median duration of 3 years of antiretroviral therapy (ART) at the time of their enrollment in the cohort study. METHODS: Wasting and stunting at ART initiation and enrollment were defined as weight-for-height/body mass index-for-age Z scores < -2 and height-for-age Z scores < -2, respectively. Logistic regression was used to assess risk factors for wasting and stunting. Main predictive factors were age at enrollment, nutritional status and age (< or ≥5 years) at ART initiation and ART duration (< or ≥3 years on first-line, or ≥3 years including a switch to second-line ART). RESULTS: Two hundred forty-four children 2-16 years of age were enrolled. Overall, wasting and stunting prevalence dropped off consistently in children 2-10 years of age, between ART initiation and enrollment, while it remained at high levels, 52% and 42%, respectively, in children 10-16 years of age. Risk factors for wasting at enrollment were ART duration of ≥3 years including a switch to second-line [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.7-8.9] and wasting at ART initiation (aOR: 2.7, 95% CI: 1.4-5.2). The risk factor for stunting at enrollment was stunting at ART initiation (aOR: 11.6, 95% CI: 5.4-25.0), independent of ART duration. CONCLUSIONS: Malnutrition at the time of ART initiation was the main predictor of malnutrition at enrollment among HIV-infected children on ART. Longer duration on ART had no overall protective effect on wasting and stunting. Growth and virologic monitoring are of utmost importance in the comprehensive care of children with HIV infection.
