Acute fatty liver of pregnancy (AFLP) is an obstetric emergency characterized by maternal liver failure and may have complications for the mother and fetus, including death. This review examines recent literature on the epidemiology, pathogenesis, diagnosis, and treatment of acute fatty liver of pregnancy. Pathogenesis of this disease has been linked to defects in fatty acid metabolism during pregnancy, especially in the setting of fetal genetic defects in fatty acid oxidation. The value of screening all patients for these genetic defects remains to be determined. Distinguishing AFLP from other high-risk liver diseases of pregnancy that have overlap features, such as HELLP and preeclampsia, can be challenging. Although sensitive diagnostic tools such as the Swansea criteria have been developed, further work is needed to diagnose AFLP more quickly. Although survival rates have improved in the past 30 years, delay in diagnosis and treatment of AFLP has life-threatening consequences; an algorithmic approach to AFLP may be a valuable resource for clinicians. Future epidemiological and long-term studies will improve our prediction of women at risk for developing AFLP and determine the long-term consequences of this condition.

No abstract

Background The presence of histone 3 lysine 9 (H3K9) methylation on the mouse inactive X chromosome has been controversial over the last 15 years, and the functional role of H3K9 methylation in X chromosome inactivation in any species has remained largely unexplored.ResultsHere we report the first genomic analysis of H3K9 di- and tri-methylation on the inactive X: we find they are enriched at the intergenic, gene poor regions of the inactive X, interspersed between H3K27 tri-methylation domains found in the gene dense regions. Although H3K9 methylation is predominantly non-genic, we find that depletion of H3K9 methylation via depletion of H3K9 methyltransferase Set domain bifurcated 1 (Setdb1) during the establishment of X inactivation, results in failure of silencing for around 150 genes on the inactive X. By contrast, we find a very minor role for Setdb1-mediated H3K9 methylation once X inactivation is fully established. In addition to failed gene silencing, we observed a specific failure to silence X-linked long-terminal repeat class repetitive elements.ConclusionsHere we have shown that H3K9 methylation clearly marks the murine inactive X chromosome. The role of this mark is most apparent during the establishment phase of gene silencing, with a more muted effect on maintenance of the silent state. Based on our data, we hypothesise that Setdb1-mediated H3K9 methylation plays a role in epigenetic silencing of the inactive X via silencing of the repeats, which itself facilitates gene silencing through alterations to the conformation of the whole inactive X chromosome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-016-0064-6) contains supplementary material, which is available to authorized users.

Objective To identify candidate genes and genetic variants for preeclampsia using a bioinformatic approach to extract and organize genes and variants from the published literature. Methods Semantic data mining and natural language processing were used to identify articles from the published literature meeting criteria for potential association with preeclampsia. Articles were manually reviewed by trained curators. Cluster analysis was used to aggregate the extracted genes into gene sets associated with preeclampsia or severe preeclampsia, early or late preeclampsia, maternal or fetal tissue sources, and concurrent conditions (i.e., fetal growth restriction (FGR), gestational hypertension, or hemolysis, elevated liver enzymes, and low platelet count). Gene ontology was used to organize this large group of genes into ontology groups. Results From more than 22 million records in PubMed, with 28,000 articles on preeclampsia, our data mining tool identified 2,300 articles with potential genetic associations with preeclampsia-related phenotypes. After curation, 729 articles were “accepted” that contained ‘statistically significant’ associations with 535 genes. We saw distinct segregation of these genes by severity and timing of preeclampsia, by maternal or fetal source, and with associated conditions (e.g., gestational hypertension, fetal growth restriction, or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome). Conclusion The gene sets and ontology groups identified through our systematic literature curation indicate that preeclampsia represents several distinct phenotypes, with distinct and overlapping maternal and fetal genetic contributions.