Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK

Maria Bejerholm Boelman, Thomas van Overeem Hansen, Matthias Nybro Smith, Sophia Hammer-Hansen, Alex Hørby Christensen, Birgitte Rode Diness*

*Corresponding author for this work

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Abstract

Pathogenic variants in several genes involved in the function or regulation of smooth muscle cells (SMC) are known to predispose to congenital heart disease and thoracic aortic aneurysm and dissection (TAAD). Variants in MYLK are primarily known to predispose to TAAD, but a growing body of evidence points toward MYLK also playing an essential role in the regulation of SMC contraction outside the aorta. In this case report, we present a patient with co-occurrence of persistent ductus arteriosus (PDA) and thoracic aortic dissection. Genetic analyses revealed a novel splice acceptor variant (c.3986-1G > A) in MYLK, which segregated with disease in the family. RNA-analyses on fibroblasts showed that the variant induced skipping of exon 24, which resulted in an in-frame deletion of 101 amino acids. These findings suggest that MYLK-associated disease could include a broader phenotypic spectrum than isolated TAAD, including PDA and obstructive pulmonary disease. Genetic analyses could be considered in families with TAAD and PDA or obstructive pulmonary disease.

Original languageEnglish
Article numbere63458
JournalAmerican Journal of Medical Genetics, Part A
Volume194
Issue number3
Number of pages6
ISSN1552-4825
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

Keywords

  • Aortic dissection
  • Aortopathy
  • Functional analyses

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