Identification of a novel pathogenic variant in MYLK in an Iranian family with non-syndromic familial aortic aneurysm and dissection by whole-exome sequencing and literature review

Germline frameshift *MYLK* variant with premature stop codon and nonsense-mediated decay

Exome sequencing of an Iranian family with non-syndromic familial thoracic aortic aneurysm and dissection (ns-FTAAD) identified a novel germline MYLK variant, NM_053025.4:c.2208_2230dup (p.Ile744Argfs9), causing a premature stop codon and nonsense-mediated decay. Five individuals were carriers and three non-carriers, segregating with disease. A comprehensive review of 1,440 TAAD patients identified 59 MYLK variant carriers (34 variants), predominantly missense (58.8%) but with a notable share of loss-of-function mechanisms (frameshift 14.7%). This work expands the mutational landscape of MYLK*-related ns-FTAAD.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

ns-FTAAD is a setting where gene identification directly informs the surgical threshold and family surveillance, hence a real clinical impact. Segregation is convincing and the systematic review provides a useful framework, although the family cohort remains modest. MYLK is already covered by pan-genomic analyses; the contribution here is documenting a loss-of-function mechanism and enriching pathogenicity data.