Coil embolization of arterioportal fistula complicated by gastrointestinal bleeding after Caesarian section: A case report.

Background: Most intrahepatic arterioportal fistulae (IAPF) are acquired. The few cases of congenital fistulae are diagnosed in infants and children.

Case Summary: We report a 31-year-old female patient presenting with haematemesis and melena three weeks after delivering her second child.

A contiguous microdeletion syndrome at Xp23.13 with non-obstructive azoospermia and congenital cataracts.

Non-obstructive azoospermia accounts for 10-15% of male infertility, resulting in 60% of all cases of azoospermia and affecting about 1% of the male population. About 30% of these cases are due to Y chromosome microdeletions, chromosome abnormalities, or hormonal disorders. Pathogenic variants in genes on the sex chromosomes have key roles in spermatogenic failure.

Exploring the landscape of pathogenic genetic variation in the ExAC population database: insights of relevance to variant classification.

Purpose: We evaluated the Exome Aggregation Consortium (ExAC) database as a control cohort to classify variants across a diverse set of genes spanning dominant and recessively inherited disorders.

Methods: The frequency of pathogenic variants in ExAC was compared with the estimated maximal pathogenic allele frequency (MPAF), based on the disease prevalence, penetrance, inheritance, allelic and locus heterogeneity of each gene. Additionally, the observed carrier frequency and the ethnicity-specific variant distribution were compared between ExAC and the published literature.

Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene.

Epigenetic mechanisms mediating expression of the Runt-related transcription factor Runx2 are critical for controlling its osteogenic activity during skeletal development. Here, we characterized bona fide regulatory elements within 120 kbp of the endogenous bone-related Runx2 promoter (P1) in osteoblasts by genomic DNase I footprinting and chromatin immuno-precipitations (ChIPs). We identified a ~10 kbp genomic domain spanning the P1 promoter that interacts with acetylated histones H3 and H4 reflecting an open chromatin conformation in MC3T3 osteoblasts.

High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms.

Genetic diagnosis of primary immune deficiencies.

Gene testing in primary immune deficiencies (PIDs) once was limited to expert academic laboratories, but now is easily available to physicians with a broad range of clinical expertise. Such testing can establish or confirm a suspected diagnosis and also may predict future disease risk in advance of clinical signs and symptoms, inform reproductive decision making, and guide clinicians in selecting the most appropriate therapeutic options. This article, based on the authors' experience and a review of the published literature, discusses some of the advances and challenges currently encountered in the clinical molecular genetic diagnosis of PIDs.

Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression.

Both activating and null mutations of proteins required for canonical WNT signaling have revealed the importance of this pathway for normal skeletal development. However, tissue-specific transcriptional mechanisms through which WNT signaling promotes the differentiation of bone-forming cells have yet to be identified. Here, we address the hypothesis that canonical WNT signaling and the bone-related transcription factor RUNX2/CBFA1/AML3 are functionally linked components of a pathway required for the onset of osteoblast differentiation.

The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts.

The Runx2 (CBFA1/AML3/PEBP2alphaA) transcription factor promotes skeletal cell differentiation, but it also has a novel cell growth regulatory activity in osteoblasts. We addressed here whether Runx2 activity is functionally linked to cell cycle-related mechanisms that control normal osteoblast proliferation and differentiation. We found that the levels of Runx2 gene transcription, mRNA and protein, are each up-regulated with cessation of cell growth (i.

Functional characterization of a human histone gene cluster duplication.

Histones are the major protein component of nucleosomes, and de novo histone synthesis is essential for packaging newly replicated DNA into chromatin. As a result, histone gene expression is exquisitely and functionally coupled with DNA replication. Vastly divergent organisms such as yeast, fly and human all demonstrate the phylogenetically conserved propensity to maintain clustering of histone genes at one or more genomic loci.

Identification of HiNF-P, a key activator of cell cycle-controlled histone H4 genes at the onset of S phase.

At the G(1)/S phase cell cycle transition, multiple histone genes are expressed to ensure that newly synthesized DNA is immediately packaged as chromatin. Here we have purified and functionally characterized the critical transcription factor HiNF-P, which is required for E2F-independent activation of the histone H4 multigene family. Using chromatin immunoprecipitation analysis and ligation-mediated PCR-assisted genomic sequencing, we show that HiNF-P interacts with conserved H4 cell cycle regulatory sequences in vivo.

Maintenance of open chromatin and selective genomic occupancy at the cell cycle-regulated histone H4 promoter during differentiation of HL-60 promyelocytic leukemia cells.

During the shutdown of proliferation and onset of differentiation of HL-60 promyelocytic leukemia cells, expression of the cell cycle-dependent histone genes is downregulated at the level of transcription. To address the mechanism by which this regulation occurs, we examined the chromatin structure of the histone H4/n (FO108, H4FN) gene locus. Micrococcal nuclease, DNase I, and restriction enzymes show similar cleavage sites and levels of sensitivity at the H4/n locus in both proliferating and differentiated HL-60 cells.

Transcriptional induction of the osteocalcin gene during osteoblast differentiation involves acetylation of histones h3 and h4.

The remodeling of chromatin is required for tissue-specific gene activation to permit interactions of transcription factors and coregulators with their cognate elements. Here, we investigate the chromatin-mediated mechanisms by which the bone-specific osteocalcin (OC) gene is transcriptionally activated during cessation of cell growth in ROS 17/2.8 osteosarcoma cells and during normal osteoblast differentiation.

P element-mediated duplications of genomic regions in Drosophila melanogaster.

Previously we have described highly unstable yellow mutations induced by chimeric elements that consist of genomic sequences originating from different regions of the X chromosome flanked by identical copies of an internally deleted 1.2 kb P element. To study further the origin and the mechanism of formation of chimeric mobile elements, we analyzed complex y-sc mutations, induced by inversions between P elements located in the neighboring yellow and scute loci.