Novel MYH11 Splice Site Variant Causing Exon Skipping in a Family With Thoracic Aortic Aneurysms and Dissections

Background MYH11 variants are associated with thoracic aortic aneurysms and dissections (TAADs) whether or not in combination with patent ductus arteriosus (PDA). MYH11 encodes vascular smooth muscle cell‐specific myosin heavy chain (MHC), and disruptions in this protein are thought to impair cellular function through disturbed intracellular force generation and altered mechanotransduction. Disease expression is characterized by incomplete penetrance and variable expression, emphasizing the complexity of inheritance and the importance of surveillance of all carriers, regardless of disease severity. Methods and Results This case report outlines a multigenerational family affected by a history of TAADs with a new recurrent MYH11 splice site variant (NM 002474.3): c.4599 + 1G > A. We report that clinical manifestations of this new variant may result in diverse phenotypic presentations, ranging from asymptomatic aortic dilatation to acute aortic dissection. Transcript analysis of patient stem cell–derived smooth muscle cells shows Exon 32 skipping, which was also previously reported in four other TAAD/PDA families with similar variants. Conclusion We report a novel MYH11 splice site variant (c.4599 + 1G > A) in a multigenerational Dutch family resulting in Exon 32 skipping through alternative pre‐mRNA splicing. This finding expands the known genetic spectrum of TAAD and enables early identification of at‐risk carriers, facilitating genotype–phenotype correlation studies and informed clinical management.