Ann Hum Genet. 2026 Oct 18. doi: 10.1111/ahg.70064. Online ahead of print.
ABSTRACT
AIMS: Thoracic aortic aneurysms and dissections are major causes of sudden cardiovascular death. We aimed to evaluate the clinical significance of the MYLK c.4079G>A, p.(Gly1360Asp) variant in Finnish families with heritable thoracic aortic disease (HTAD) and to assess evidence for a potential founder effect.
METHODS: We evaluated the clinical significance and potential founder effect of the missense variant MYLK c.4079G>A, p.(Gly1360Asp) in Finnish families. Eight individuals from four unrelated Finnish families carrying the MYLK c.4079G>A heterozygous variant were recruited. Clinical histories, imaging data, and pedigrees were reviewed. Genetic testing included exome‑based gene panel sequencing or targeted familial variant testing. Variant classification followed the American College of Medical Genetics and Genomics 2015 guidelines.
RESULTS: Thoracic aortic dilatation or aneurysm occurred in 6/8 carriers (75%), with a mean age at diagnosis of 45 years (range 34-67). Ascending aortic diameters ranged from 26-59 mm, most often measured at the aortic root. Aortic dissection occurred in 4/8 (50%) at a mean age of 46 years (range 34-68), including three early‑adult events. Extrathoracic arterial involvement (carotid) was observed in one variant‑positive individual.
CONCLUSION: The MYLK c.4079G>A, p.(Gly1360Asp) variant was present in six affected individuals from four unrelated families and is enriched in the Finnish population, supporting a founder effect. The MYLK c.4079G>A, p.(Gly1360Asp) variant is associated with early‑adult‑onset, high‑penetrance thoracic aortic disease and substantial dissection risk, underscoring the need for vigilant surveillance and early intervention in affected individuals and at‑risk relatives.
PMID:42892740 | DOI:10.1111/ahg.70064