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

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...

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Bibliographic Details
Published in:	American journal of medical genetics. Part A Vol. 194; no. 3; pp. e63458 - n/a
Main Authors:	Boelman, Maria Bejerholm, Hansen, Thomas van Overeem, Smith, Matthias Nybro, Hammer‐Hansen, Sophia, Christensen, Alex Hørby, Diness, Birgitte Rode
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-03-2024 Wiley Subscription Services, Inc
Subjects:	Aorta Aortic Aneurysm, Thoracic - diagnosis Aortic Aneurysm, Thoracic - genetics Aortic aneurysms Aortic dissection Aortic Dissection - genetics Aortopathy Azides Calcium-Binding Proteins - genetics Deoxyglucose - analogs & derivatives Dissection Ductus Arteriosus - diagnostic imaging Ductus Arteriosus - metabolism Ductus Arteriosus - pathology Ductus Arteriosus, Patent - genetics Functional analyses Genetic analysis Heart diseases Humans Lung diseases Lung Diseases, Obstructive Male Myosin-Light-Chain Kinase - genetics Myosin-Light-Chain Kinase - metabolism Obstructive lung disease Pedigree Smooth muscle Thorax Aortic dissection Aortopathy Functional analyses
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Summary:	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.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Report-1
ISSN:	1552-4825 1552-4833 1552-4833
DOI:	10.1002/ajmg.a.63458