Molecular Mechanisms of ZIKV-Induced Teratogenesis: A Systematic Review of Studies in Animal Models.

Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos. Moreover, few literature reviews have been conducted with these studies. The aim of this systematic review is to evaluate the molecular mechanisms of ZIKV teratogenesis determined from studies in animal models. PubMed/MEDLINE, EMBASE, Web of Science, and Scopus as well as grey literature were searched for studies that evaluated molecular alterations related to ZIKV teratogenesis which occurred during embryonic development. Nine studies were included: six with mice, one with mice and guinea pigs, one with pigs and one with chickens. In general, studies presented an unclear or high risk of bias for methodological criteria. Most of studies reported embryos exposed to ZIKV presenting microcephaly, reduced cortex thickness, and growth restriction. Different techniques were used to evaluated molecular changes in the animals following ZIKV infection: RNA sequencing, RT-qPCR, and in situ hybridization. It was found that common pathways are changed in most studies, being pathways related to immune response upregulated and those involved to neurodevelopment downregulated.

Intrafamilial clinical variability in four families with incontinentia pigmenti.

Incontinentia Pigmenti (IP) is an X-linked rare genodermatosis caused by mutations in the IKBKG gene, which is essential to NF-κB pathway activation and thus fundamental for cell survival. Our objective was to study the intrafamilial clinical variability in IP by investigating how the signs of IP, and especially dental anomalies, vary within affected families. Four families, encompassing a total of 15 IP familial cases, were included in the study. The patients were subjected to clinical examination and collection of family histories for assessment of intrafamilial clinical variability. All familial cases carried the IKBKGdel recurrent deletion. A noticeable intrafamilial clinical variability was observed in all studied families, with mild and severe cases co-occurring within a same family. Additionally, to best of our knowledge, our study was the first to address the variability of dental defects within IP families, and here too, our results reveal remarkable differences among affected relatives. A number of as yet unidentified genes might act as modifiers, influencing disease expressivity. Our study found important clinical variability within four IP families and contributes to the understanding of the genetic background involved in IP expressivity.