2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Proof of Concept Core Biopsy Technique of Vascular Malformations for DNA and RNA Sequencing with Novel Identification of <em>PKD1 </em>Variant

Pdf Summary

In this study, the researchers aimed to evaluate the feasibility and safety of taking multiple core biopsies of vascular malformation (VM) tissue in patients, assess the quality of the core biopsy tissue for histopathological, immunohistochemical, and molecular evaluation, and analyze the DNA and RNA sequencing of VM tissue for known and potential novel variants associated with VM.<br /><br />Vascular malformations are abnormal formations of blood vessels that occur during early vascular development. Somatic gene variants are believed to be the main cause of VM, with occasional germline variants also identified. The current treatment approach for VM is based on factors such as size, location, and flow characteristics, rather than molecular mechanisms. Access to VM tissue is limited, making it difficult to understand the molecular mechanisms and develop targeted treatments.<br /><br />In this study, two patients with spontaneous slow-flow VM underwent ultrasound-guided core biopsies of their VM tissue. The biopsy samples were then processed for histopathology, immunohistochemistry, DNA sequencing, and RNA sequencing. The results showed that multiple core biopsies of VM tissue can be safely performed and yield adequate tissue for evaluation. Genome sequencing of the VM tissue has the potential to identify known and novel variants associated with VM pathogenesis.<br /><br />One interesting finding of this study was the identification of a variant in the PKD1 gene within the VM tissue of one patient. Pathogenic germline variants in PKD1 are known to cause autosomal dominant polycystic kidney disease (ADPKD), but to the researchers' knowledge, these variants have not been previously identified within VM tissue or associated with peripheral VM. Further characterization of this PKD1 variant is needed to determine its pathogenicity.<br /><br />Overall, this pilot study provides a basis for larger-scale VM core biopsy validation in order to further understand the molecular mechanisms of VM and develop new therapeutic strategies.

Asset Subtitle

Presenting Author - Whitney Thompson, M.D. M.Phil; Co-Author - Eric Klee; Co-Author - Brendan Lanpher, MD; Co-Author - Emily Bendel, MD; Co-Author - Megha Tollefson, MD; Co-Author - Scott Thompson, MD PhD;

Meta Tag

Bioinformatics

Cardiovascular System

Etiology

Genetic Testing

Genome sequencing

Identification of Disease Genes

Malformation

NextGen Sequencing

Pathogenesis

Pathology

Phenotype

Sequencing

Variant Detection

Co-Author Eric Klee

Co-Author Brendan Lanpher, MD

Co-Author Emily Bendel, MD

Co-Author Megha Tollefson, MD

Co-Author Scott Thompson, MD PhD

Presenting Author Whitney Thompson, M.D. M.Phil

Keywords

vascular malformation

core biopsies

feasibility

safety

DNA sequencing

RNA sequencing

gene variants

molecular mechanisms

targeted treatments

PKD1 gene