Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK
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Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK. / Boelman, Maria Bejerholm; Hansen, Thomas van Overeem; Smith, Matthias Nybro; Hammer-Hansen, Sophia; Christensen, Alex Hørby; Diness, Birgitte Rode.
In: American Journal of Medical Genetics, Part A, Vol. 194, No. 3, e63458, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK
AU - Boelman, Maria Bejerholm
AU - Hansen, Thomas van Overeem
AU - Smith, Matthias Nybro
AU - Hammer-Hansen, Sophia
AU - Christensen, Alex Hørby
AU - Diness, Birgitte Rode
N1 - Publisher Copyright: © 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Aortic dissection
KW - Aortopathy
KW - Functional analyses
U2 - 10.1002/ajmg.a.63458
DO - 10.1002/ajmg.a.63458
M3 - Journal article
C2 - 37921548
AN - SCOPUS:85175863386
VL - 194
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
M1 - e63458
ER -
ID: 383704925