Identification of 17q12 microdeletion syndrome in a Latin American patient with maturity-onset diabetes of the young subtype 5: a case report.

BACKGROUND: Maturity-onset diabetes of the young comprises a large group of autosomal inherited gene mutations. Maturity-onset diabetes of the young subtype 5 is caused by mutations in the HNF1B gene. This gene is expressed in the early phase of embryonic development in the pancreas, kidneys, liver, and genital tract; therefore, kidney or urinary tract malformations are associated with diabetes mellitus. The 17q12 deletion syndrome is a cause of maturity-onset diabetes of the young subtype 5 that should be considered. CASE PRESENTATION: We present the case of a 35-year-old Hispanic female patient with a history of bicornuate uterus and polycystic renal disease that required kidney transplant. She had insulin-dependent diabetes, with her mother, maternal grandmother, and great-grandmother showing a similar clinical manifestation. Molecular analysis showed a deletion in chromosome 17q12 involving 15 genes, including HNF1B. Therefore, a diagnosis of deletion syndrome was made. CONCLUSIONS: The 17q12 deletion syndrome represents a rare genetic syndrome that involves different genes, including HNF1B. Principally, it is characterized by the combination of genitourinary tract malformations and diabetes mellitus, similar to our patient.

RUNX1 gene expression changes in the placentas of women smokers.

The placenta can be affected by environmental factors, such as exposure to cigarette smoke. This exposure in the fetal context is considered a risk factor for the development of short-term postnatal diseases, such as asthma. Asthma is an inflammatory disease characterized by predominant acquisition of CD4 T lymphocytes (TLs) of the Th2 type. Transcription factors such as GATA binding protein 3 (GATA3) and STAT6 actively participate in the differentiation of virgin TLs towards the Th2 profile, while transcription factors such as STAT1, T-Box transcription factor 21 (T-BET), RUNX1 and RUNX3 participate in their differentiation towards the Th1 profile. The objective of the current study was to evaluate the impact of exposure to cigarette smoke on the gene expression of STAT1, T-BET, GATA3, IL-4, RUNX1 and RUNX3 during the gestation period, and to determine whether the expression levels of these genes are associated with changes in global methylation. STAT1, GATA3, RUNX1 and RUNX3 protein and mRNA expression levels in the placental tissue of women smokers and non-smoking women were determined via immunohistochemistry and quantitative PCR (qPCR) respectively. Additionally, T-BET and IL-4 mRNA expression levels were determined by qPCR. On the other hand, global methylation was determined via ELISA. In the present study, significant increases were observed in RUNX1 transcription factor expression in placentas from women smokers when compared with placentas of non-smoking women. Similarly, significant increases in the expression of GATA3, IL-4 and RUNX3 mRNA were observed. The changes in gene expression were not associated with changes in the global methylation levels. Finally, a higher frequency of low-birth-weight infants were identified in cases of exposure to cigarette smoke during pregnancy when compared with infants not exposed to cigarette smoke during pregnancy. Thus, the data of the present study contributed to the understanding of the genetic and clinical impacts of exposure to cigarette smoke during pregnancy and its importance in maternal and fetal health.

Characterization of Risk Factors for Neural Tube Defects: A Case-Control Study in Bogota and Cali, Colombia, 2001-2018.

Worldwide prevalence of neural tube defects is between 1.2 and 124.1 per 10 000 live births. This study analyzes risk factors linked with neural tube defects. The study focused on the Surveillance and Monitoring Programs of Congenital Anomalies databases in Bogota and Cali. Births were monitored between 2001 and 2018. Liveborn or stillborn with neural tube defects were defined as cases, using a case-control ratio of 1:4. Paternal age, folic acid supplementation, birth weight, urban or rural origin, maternal and paternal studies, and socioeconomic levels were analyzed. Across the 215 730 births monitored, 147 cases with a rate of 6.82/10 000 live births were found (6.79-6.85). In isolated cases, lower birth weight had a P <.01. Paternal age >45 years showed an odds ratio (OR) of 4.24 (1.54-11.65), socioeconomic status 1 and 2, OR of 2.49 (1.63-3.82), maternal primary schooling or lower OR 2.61 (1.28-5.31), and housing in urban areas OR 2.4 (1.4-4.09).

Impact of umbilical cord length on fetal circulatory system by Doppler assessment.

INTRODUCTION: Numerous studies have revealed the impact of umbilical cord (UC) length on fetal perfusion; abundant data implicate abnormal UC length to neurological delay and subsequent poor prognoses for fetuses and newborns. Indeed, our group previously developed theoretical approximations that contributed to formulas capable of explaining the impact of UC length on cardiac output. METHODS: We performed an observational study that measured the pulsatility index and flow velocity in umbilical arteries. A special Doppler measured proximal and distal indexes in both arteries. After birth, medical staff measured complete UC length. We obtained maternal and neonatal outcomes from clinical records. RESULTS: Our study enrolled 20 pregnant mothers. We found that flow velocities in the two edges were different: fetal edges exhibited greater velocity in the majority of cases; but, when we compared pressure differentials (ΔP), the pulsatility index was significantly related to umbilical cord length. CONCLUSIONS: Fetal perfusion, welfare, and viability are related to UC function as the conveyor of all fetal volemia. Excessive UC length affects cardiac dynamics and increases peripheral vascular resistance. Further studies could validate routine use of the differential proximal and distal measurements proposed in this article, and their implications in in utero fetal heart function. We also hope that early diagnosis or UC alterations could alert neonatologists and obstetricians to clinical conditions of the fetus.

Transición epitelio mesénquima: de lo molecular a lo fisiológico / Epitelial Mesenchymal Transition: From the Molecular to Physiologic

La transición epitelio mesénquima (EMT) es un proceso compuesto de diferentes fases, donde una célula epitelial adquiere un fenotipo mesenquimal. Dentro de los cambios involucrados se encuentran: pérdida de la polaridad celular, adquisición de una capacidad migratoria, capacidad invasora, resistencia a la apoptosis y aumento en la producción de componentes de la matriz extracelular. Todos estos cambios ocurren como una consecuencia de la activación y represión de genes involucrados con rutas de señalización específicas relacionadas con este evento. La EMT está relacionada con procesos fisiológicos y patológicos como el cáncer. Consta de tres fases: una de células no migratorias, células premigratorias y células migratorias; cada una de ellas producto de diferentes señales intra o extracelulares, factores de transcripción (TGF-B, Snail, TWIST, Sox, Slug, ZEB1, entre otras) y proteínas involucradas (E-cadherina, integrina, vimentina, ocludinas y claudinas).

Transition mesenchymal epithelium (EMT) is a process composed of different phases where an epithelial cell acquires a mesenchymal phenotype. Among the changes involved are: loss of cellular polarity, acquisition of a migratory capacity, invasive capacity, resistance to apoptosis, and increase in the production of components of the extracellular matrix. All these changes occur as a consequence of the activation and repression of genes involved with specific signaling pathways related to this event. EMT is related to physiological and pathological processes such as cancer. It consists of three phases: A phase of non-migratory cells, pre-migratory cells and migratory cells; (TGF-B, Snail, TWIST, Sox, Slug, ZEB1 among others), and proteins involved (E-cadherin, integrin, vimentin, occludins and claudins).