2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A Comparative Analysis of <em>TEK</em> Variants in Patients with Vascular Anomalies

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This study focused on profiling TEK variants in patients with somatic vascular anomalies (SVA), which are characterized by abnormal blood vessels in the skin and internal organs. The TEK gene encodes the Tie2 receptor tyrosine kinase, which plays a role in regulating the vascular system. Variations in TEK have been linked to the development of SVA. <br /><br />The researchers identified five patterns of TEK variants based on their distribution and occurrence in patients. Pattern 1 involved a pathogenic variant accompanied by another pathogenic or likely pathogenic variant, often appearing earlier in the disease progression or in the germline. Pattern 2 involved variations at codon Tyr897, sometimes accompanied by variations at codon Arg915 or Arg918. Pattern 3 involved the most frequently altered codon, Leu914, which often occurred as a single variant. Pattern 4 involved cases with single variants in codon Arg915 or Arg918. Pattern 5 involved variants at the C-terminal end of the Tie2 protein, with doublets tending to occur in cis.<br /><br />The majority of TEK variants identified in SVA patients were pathogenic or likely pathogenic, and a quarter of patients had two pathogenic or likely pathogenic variants. The majority of the variants occurred in the tyrosine kinase (TK) domain of the Tie2 protein. <br /><br />The study also highlighted three hotspot regions of the TEK gene: codon Arg849, which is a predisposition variant in SVA; the region spanning codons 897-918, which is the most frequently mutated region in SVAs; and the region spanning codons 1094-1113, which can drive disease pathogenesis even when occurring as single variants. <br /><br />Overall, this study provides insights into the distribution and frequency of TEK variants in patients with SVA, shedding light on the genetic factors involved in the development of this vascular anomaly. Further research is needed to understand the underlying mechanisms and develop effective treatments for SVA.

Asset Subtitle

Presenting Author - Reza Ghasemi, Ph.D.; Co-Author - Meagan M. Corliss, Master; Co-Author - Kilannin A. Krysiak, PhD; Co-Author - Bijal Parikh, MD, PhD; Co-Author - Alexa M. Dickson, PhD; Co-Author - Kevin M. Bowling; Co-Author - Molly C. Schroeder, PhD, FACMG; Co-Author - Jonathan W. Heusel, MD, PhD; Co-Author - Julie A. Neidich, MD; Co-Author - Yang Cao, PhD, FACMG;

Meta Tag

Genetic Testing

Malformation

Molecular Pathophysiology

NextGen Sequencing

Pathogenesis

Pathology

Sequencing

Variant Detection

Co-Author Meagan M. Corliss, Master

Co-Author Kilannin A. Krysiak, PhD

Co-Author Bijal Parikh, MD, PhD

Co-Author Alexa M. Dickson, PhD

Co-Author Kevin M. Bowling

Co-Author Molly C. Schroeder, PhD, FACMG

Co-Author Jonathan W. Heusel, MD, PhD

Co-Author Julie A. Neidich, MD

Co-Author Yang Cao, PhD, FACMG

Presenting Author Reza Ghasemi, Ph.D.

Keywords

TEK variants

somatic vascular anomalies

abnormal blood vessels

Tie2 receptor tyrosine kinase

regulating the vascular system

development of SVA

pathogenic variant

codon variations

tyrosine kinase domain

genetic factors