We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Technopath Clinical Diagnostics - An LGC Company

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Whole Genome Sequences Discriminate Hereditary Hemorrhagic Telangiectasia Phenotypes

By LabMedica International staff writers
Posted on 26 Jul 2022
Print article
Image: This photograph shows a close-up of the face of a patient with multiple telangiectasias secondary to hereditary hemorrhagic telangiectasia (Photo courtesy of Dr. P. Marazzi)
Image: This photograph shows a close-up of the face of a patient with multiple telangiectasias secondary to hereditary hemorrhagic telangiectasia (Photo courtesy of Dr. P. Marazzi)

The abnormal vascular structures of hereditary hemorrhagic telangiectasia (HHT) often cause severe anemia due to recurrent hemorrhage, but HHT causal genes do not predict the severity of hematological complications.

Telangiectasia and larger arteriovenous malformations (AVMs) are characterized by defective vascular walls predisposing to hemorrhage. Individuals affected by HHT experience spontaneous, recurrent nosebleeds due to abnormal nasal vasculature and exhibit small, visible telangiectatic vessels that tend to develop on the lips, oral cavity, and finger pads.

Medical Scientists at the Imperial College School of Medicine (London, UK) tested for chance inheritance and clinical associations of rare deleterious variants in which loss-of-function causes bleeding or hemolytic disorders in the general population. In double-blinded analyses, all 104 patients with HHT from a single reference center recruited to the 100,000 Genomes Project were categorized on new MALO (more/as-expected/less/opposite) sub-phenotype severity scales, and whole genome sequencing data were tested for high impact variants in 75 HHT-independent genes encoding coagulation factors, or platelet, hemoglobin, erythrocyte enzyme, and erythrocyte membrane constituents.

Genes were primarily selected based on causal influences on coagulation, hemorrhage, and/or red blood cell (erythrocyte) survival exposed in the general population by bleeding disorders or congenital hemolytic anemias. The burden of usual genetic variation was compared between genes and gene categories using the gene damage index and by genic intolerance measured by the residual variation intolerance score. Variant deleteriousness was ranked by Combined Annotation Depletion (CADD) scores.

The team reported that rare variants (all gnomAD allele frequencies <0.003) were identified in 56 (75%) of these 75 HHT-unrelated genes. Deleteriousness assignments by Combined Annotation Dependent Depletion (CADD) scores >15 were supported by gene-level mutation significance cutoff scores. CADD >15 variants were identified in 38/104 (36.5%) patients with HHT, found for 1/10 patients within platelet genes; 1/8 within coagulation genes; and 1/4 within erythrocyte hemolytic genes. In blinded analyses, patients with greater hemorrhagic severity that had been attributed solely to HHT vessels had more CADD-deleterious variants in platelet and coagulation genes. However, the HHT cohort had 60% fewer deleterious variants in platelet and coagulation genes than expected.

The authors concluded that the potential to unmask pathophysiologically relevant processes is augmented by categorizing patients using severity scales that additionally influence risk-benefit considerations inherent in therapeutic provision. The study was published on July 7, 2022 in the journal Blood Advances.

Related Links:
Imperial College School of Medicine 

New
Gold Supplier
Body Fluid Application
CellaVision Body Fluid Application
New
Silver Supplier
Point-of-Care MDx System
STANDARD M10
New
Infliximab Rapid Test
Quantum Blue Infliximab
New
Silver Supplier
Urea Breath Test
13C-Urea Breath Test

Print article

Channels

Molecular Diagnostics

view channel
Image: The new multiplex QIAstat-Dx Viral Vesicular Panel is designed to support research and surveillance efforts (Photo courtesy of QIAGEN)

First Syndromic Test Differentiates Between Monkeypox and Five Pathogens with Similar Symptoms

A new syndromic test differentiates between monkeypox and five other pathogens which cause similar symptoms. This first-ever test detects the two known forms of monkeypox virus (the so-called West African... Read more

Industry

view channel
Image: The Accelerate Arc Module & BC kit is registered as an IVD (Photo courtesy of Accelerate Diagnostics)

BD and Accelerate Diagnostics Collaborate to Offer Rapid Antimicrobial Identification and Susceptibility Diagnostics

Becton, Dickinson and Company (BD, Franklin Lakes, NJ, USA) and Accelerate Diagnostics, Inc. (Tucson, AZ, USA) have entered into a worldwide commercial collaboration agreement where BD will offer Accelerate's... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.