Shin Yi Jang

Abstract Marfan syndrome (MFS) is a genetic disorder caused by an FBN1 variant and is diagnosed based on the revised Ghent criteria, which incorporate clinical manifestations and genetic testing. Up-to-date FBN1 variant interpretation is crucial for proper diagnosis and management of MFS; however, some FBN1 variants of uncertain significance (VUSs) remain inconclusive despite applying Clinical Genome Resource (ClinGen) FBN1-specific guideline.

1 INTRODUCTION Marfan syndrome (MFS; MIM 154700) is a systemic connective tissue disorder with a high degree phenotypic variability, ranging from mild (features of MFS in one or a few systems) to severe and even rapidly progressive neonatal multi-organ disease.1 Pathogenic variants of fibrillin-1 (FBN1; MIM 134797) which is the causative gene can lead to highly penetrant thoracic aortic aneurysms and dissections with ocular and skeletal complications.2 Currently, more than 2800 pathogenic or...

Abstract Background Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disease caused by aberrations in COL3A1, which encodes type III collagen. Sanger sequencing has limitations for diagnosis since exon deletion/duplication and splicing alterations are not uncommon in COL3A1. We report 2 patients with vEDS who were not diagnosed by conventional Sanger sequencing. Methods We performed either targeted panel or whole-genome sequencing.