Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs) in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β) signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curaçao) diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS) HHT panel is proposed.

Antifungal compound honokiol triggers oxidative stress responsive signalling pathway and modulates central carbon metabolism

“…After adding 3 μg/ml honokiol to fission yeast culture at the early time point (4 h), we characterised total 554 genes (512 genes with increased expression levels and 42 genes with decreased expression levels) whose expression levels are significantly affected by honokiol treatment (fold >2, p -value < 0.05, shown in Supplementary Table 1). We next performed the GSEA via the web-tool AnGeLi for comprehensively analysing the honokiol-modulated gene lists (Bitton et al 2015). As shown in Table 1, honokiol treatment can significantly trigger the stress-related genes’ expression.…”

“…Gene Set Enrichment Analysis (GSEA) was conducted by the online tool AnGeLi (Bitton et al 2015). The enriched gene ontology category was selected based on biological process and molecular function using list frequency >5% and p -value <0.01 as the selection criterion.…”

Habitat connectivity is determined by the scale of habitat loss and dispersal strategy

“…Similarly, and perhaps more importantly, dispersal represents one of the few routes for organisms to escape habitats that are under pressure from fragmentation (With & King, 1999). As such, the persistence of populations affected by habitat loss, including those that are genetically distinct, likely depend on individuals that can cross a matrix of hostile landscapes before reaching a suitable habitat, or use stepping‐stones in the habitat to connect with important resources (Watts et al., 2015). …”

Liver Transplantation for High Output Heart Failure Secondary to HHT: A Case Report and Review of the Literature

“…These lesions can affect the skin, nasal cavity, gastrointestinal tract, liver, lung and brain [2,3]. Symptoms depend on the location and extent of lesions with the most common presenting symptoms including epistaxis and gastrointestinal bleeding [2].…”

“…Hereditary hemorrhagic telangiectasia (HHT) (also known as OslerWeber-Rendu syndrome) is an autosomal dominant disease characterized by the presence of angiodysplastic lesions (telangiectasias and arteriovenous malformations (AVM)) that affect many organs [1,2]. These lesions can affect the skin, nasal cavity, gastrointestinal tract, liver, lung and brain [2,3].…”