2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-A novel <em>TGFBR1</em> splice-site variant identified in a family with Loeys-Dietz syndrome and variable aortic phenotypes

A novel TGFBR1 splice-site variant identified in a family with Loeys-Dietz syndrome and variable aortic phenotypes

Pdf Summary

This document presents a case report of a family with Loeys-Dietz syndrome (LDS), a genetic disorder characterized by aortic phenotypes and other associated features. The report focuses on a novel missense variant in the TGFBR1 gene, c.575G>T p.G192V, which was found in three family members who exhibited atypical features and variable expressivity of aortic phenotypes. The variant was predicted to alter gene splicing and create a novel exonic splice acceptor site. The report highlights the clinical evaluations and findings of the family members, including aortic root aneurysm, joint dislocations, myopia, joint hypermobility, craniofacial anomalies, and vascular findings such as tortuosity of the carotid arteries and aneurysms. <br /><br />The findings suggest that the spectrum of LDS is expanding, with less severe cases being identified. Cascade testing helped identify individuals harboring the variant with mild phenotypes, challenging the assumption of complete penetrance in LDS. The case emphasizes the variability of phenotypic features associated with LDS1 within a family, expanding the range and assumed severity of the condition. The splice site variant identified in this report represents a rare mechanism of LDS, as few splicing variants have been reported in the TGFBR1 gene. Understanding the variability of features and disease variants has important implications for genetic counseling and clinical management. <br /><br />The report includes clinical photos and a pedigree highlighting the variability of vascular findings within the family. Overall, the findings contribute to the understanding of LDS and the genetic mechanisms underlying the condition.

Asset Subtitle

Co-Author - Savannah Kile, BS; Presenting Author - Veronica Fettig, MS, CGC; Co-Author - Amy R. Kontorovich, MD, PhD;

Meta Tag

Cardiovascular System

Clinical History

Counseling

Genetic Testing

Genotype-Phenotype Correlations

Risk Assessment

Co-Author Savannah Kile, BS

Co-Author Amy R. Kontorovich, MD, PhD

Presenting Author Veronica Fettig, MS, CGC

Keywords

Loeys-Dietz syndrome

genetic disorder

aortic phenotypes

TGFBR1 gene

missense variant

gene splicing

exonic splice acceptor site

clinical evaluations

phenotypic features

genetic counseling