Background: Recent studies have shown that recessive mutations in the TBC1D24 gene cause a variety of epilepsy syndromes, DOORS syndrome and nonsyndromic deafness. Methods/Results: We report on two siblings with hypotonia, early-onset epileptic encephalopathy, and severe developmental delay. The patients presented with clonic and myoclonic jerks within 1 h after birth. The seizures were resistant to treatment. Audiologic examination showed bilateral sensorineural hearing loss in both siblings. Genetic analysis revealed compound heterozygous mutations in the TBC1D24 gene: a novel missense mutation c.32A ) G (p.Asp11Gly) in exon 2 and a frameshift mutation c.1008delT (p.His336Glnfs*12) in exon 4. Conclusion: This report supports previous observations that mutations in TBC1D24 cause diverse phenotypes. In fact, early-onset epileptic encephalopathy with sensorineural hearing loss is an additional phenotype observed in patients with recessive TBC1D24 mutations.
COBISS.SI-ID: 2046636
Periventricular leukomalacia (PVL) is a neonatal brain white matter injury associated with development of cerebral palsy, intellectual impairment, and visual disturbances. PVL is more common in premature neonates. Our objective was to examine the impact of several potential risk factors other than prematurity on the incidence of PVL. A case-control study based on the Slovenian National Perinatal Information System data for the period 2002-2011. All singleton and twin pregnancies delivered at ≥22 weeks' in Slovenia during the study period were included. Cases were pregnancies with PVL in at least one neonate. For each pregnancy in the case cohort, three pregnancies matched by gestational age and plurality were selected. Chi-square test was used to examine the associations between PVL and several potential risk factors: maternal age, pre-pregnancy body-mass-index, preexisting diabetes, gestational diabetes, pregnancy after in-vitro-fertilization, severe preeclampsia, vaginal delivery, no steroid therapy prior to delivery, small for gestational age, and fetal-inflammatory-response-syndrome. P(0.05 was considered statistically significant. One lakh ninety one thousand and eighty three singleton and 3377 twin pregnancies delivered at ≥22 weeks' in Slovenia during the study period. PVL was diagnosed in 86 singletons (0.045%) and 25 twins (0.74%). In all twin pregnancy cases only one twin was diagnosed with PVL. 258 singleton and 75 twin controls were matched to the 86 singleton and 25 twin cases. Of all risk factors studied, only maternal obesity and chorioamnionitis were significantly associated with PVL. Maternal obesity and chorioamnionitis increase the risk of PVL beyond that expected solely from prematurity.
COBISS.SI-ID: 2332076
Estrogens are known to selectively influence cell proliferation. Physiological variations of blood hormone concentration might play a role in regulating the level of X chromosome aneuploidy. In this study we observed the percentages of X aneuploid cells in standard lymphocyte cultures from blood samples obtained in relation to the menstrual cycle, noting whether collection occurred during either the follicular or the luteal phase. Methods: A study consisting of 28 women with X mosaicism and recurrent pregnancy loss, and 28 age-matched healthy controls. Cytogenetic studies were carried out on peripheral blood samples according to standard procedures. Results:A significant difference in the percentage of X aneuploidy was found in blood samples obtained during different phases of the menstrual cycle. In the case group, the mean value of aneuploid cells in the follicular and luteal phase samples was 10.0 and 6.3 % respectively and in the control group, it was 2.8 and 1.0 % (P ( 0.0001). The difference in the case group varied between 0 and 8 % (3.6 ± 2.1 %) and in the control group between 0 and 4 % (1.7 ± 1.1 %). The specificity for detecting true X mosaicism was 0.875. We estimate that the initial diagnosis of X mosaicism could be correct in 68 % of patients with recurrent pregnancy loss. Conclusion: This observational study establishes that the time of blood sampling in relation to the menstrual cycle can influence lymphocyte X chromosome mosaicism. The results, further proven by additional controlled studies, would have practical implications for genetic counselling and fertility treatment.
COBISS.SI-ID: 1919148
Estrogens and antioxidants indirectly alleviate telomere attrition. However, available clinical data on the association between hormone exposure and telomere length are inconclusive. In the present study, we examined the effects of exogenous estrogen use and of some genetic factors implicated in estrogen metabolism and oxidative stress response on mean leukocyte telomere length. We studied 259 postmenopausal women. Genotyping was conducted for CYP1B1 (rs1056836), COMT (rs4680), GSTP1 (rs1695), MnSOD (rs4880), KRAS (rs61764370), and MTHFR (rs1801133 and rs1801131) polymorphisms. Mean leukocyte telomere length was measured using a quantitative real-time PCR assay. In multivariate analysis we found no association between oral contraceptives or hormone replacement therapy (HRT) and mean leukocyte telomere length. The presence of variant alleles in CYP1B1, KRAS and MTHFR genes was statistically significantly associated with shorter mean leukocyte telomere length. Further, the data provided evidence for the effect modification of the association between HRT and mean leukocyte telomere length by the CYP1B1, KRAS and MTHFR genotypes. Our findings suggest that functionally relevant genetic variants within estrogen and folate metabolic pathways may influence telomere length. We propose these genetic factors should be taken into consideration when interpreting associations between hormone exposure and telomere length.
COBISS.SI-ID: 2021243