Whole-Exome Sequencing Uncovers a Novel Efemp2 Gene Variant (C.C247t) Associated With Dominant Nonsyndromic Thoracic Aortic Aneurysm Publisher Pubmed



Sadeghipour P¹ ; Valuian M² ; Ghasemi S² ; Rafiee F² ; Pourirahim M³ ; Mahmoodian M⁴ ; Maleki M³ ; Kalayinia S³ Show Affiliations
Source: Lab Medicine Published:2024

Abstract

Background: Thoracic aortic aneurysm (TAA) is a multifactorial disorder. Familial TAA, which is more clinically aggressive, is associated with a high risk of lethal dissection or rupture. Genetic evaluation can provide TAA patients with personalized treatment and help in predicting risk to family members. Objective: The purpose of this investigation was to report a likely pathogenic variant in the EFEMP2 gene that may contribute to TAA in a family with a documented history of the condition. Methods: In the index patient, the causative genetic predisposition was identified using whole-exome sequencing. The potential likely pathogenic effect of the candidate variant was further analyzed through bioinformatics analysis, homology modeling, and molecular docking. Results: The results revealed a likely pathogenic heterozygous variant, c.247C>T p.Arg83Cys, in exon 4 of the EFEMP2 gene (NM_016938), which was predicted to have disease-causing effects by MutationTaster, PROVEAN, SIFT, and CADD (phred score = 27.6). Conclusion: In this study, a likely pathogenic variant in the EFEMP2 gene was identified in an Iranian family with a dominant pattern of autosomal inheritance of TAA. This finding underscores the importance of conducting molecular genetic evaluations in families with nonsyndromic TAA and the significance of early detection of at-risk family members. © The Author(s) 2023.