Hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait and caused by loss-of-function pathogenic variants in genes encoding proteins of the BMP signalling pathway. Up to 90% of disease-causal variants are observed in ENG and ACVRL1, with SMAD4 and GDF2 less frequently responsible for HHT. In adults, the most frequent HHT manifestations relate to iron deficiency and anaemia owing to recurrent epistaxis (nosebleeds) or bleeding from gastrointestinal telangiectases.

Elective Thoracic Surgical Resections for Pulmonary Arteriovenous Malformations - A 16 Year Single-Center Experience.

Pulmonary arteriovenous malformations (PAVMs) cause cerebral abscess and ischemic stroke due to paradoxical emboli, risks that are increasingly recognized. We report the evolving placement of thoracic surgery in multi-disciplinary team management of PAVMs that were sporadic or associated with hereditary hemorrhagic telangiectasia. From 1983 to 2006, all patients receiving elective treatment had embolization.

When "loss-of-function" means proteostasis burden: Thinking again about coding DNA variants.

Each human genome has approximately 5 million DNA variants. Even for complete loss-of-function variants causing inherited, monogenic diseases, current understanding based on gene-specific molecular function does not adequately predict variability observed between people with identical mutations or fluctuating disease trajectories. We present a parallel paradigm for loss-of-function variants based on broader consequences to the cell when aberrant polypeptide chains of amino acids are translated from mutant RNA to generate mutated proteins.

Correction: Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes.

[This corrects the article DOI: 10.1371/journal.pone.