Key result
Heterozygous MYLK deletion linked to loss of protein function in a patient with extensive dissections.
Why the study?
Deletions in MYLK are rare and infrequently reported, and their molecular effects on extensive arterial dissections are not well characterized.
Case Report (n=1)
A multiomic approach including molecular modeling demonstrated that a rare MYLK deletion causes loss of kinase function, explaining the phenotype of extensive arterial dissections.
Supports MYLK loss-of-function in arterial dissections; hypothesis-generating and requires validation before clinical adoption.
We describe the phenotype of a patient with extensive aortic, carotid, and abdominal dissections. The proband was found to have a heterozygous deletion of exons 21–34 inMYLK, which is a rare finding, as deletions in this gene have been infrequently reported. We describe this finding following detection in a proband with an extensive history of aortic, carotid, and abdominal dissections. Neoteric molecular modeling techniques to help determine the impact of this deletion on protein function indicated loss of function due to lack of any kinase domain. We also provide the electrostatics calculations from the wild type and mutant variant. Through a combined multiomic approach of clinical, functional, and protein informatics, we arrive at a data fusion for determination of pathogenicity embedded within the genetic code for this particular genetic variant, which, as a platform, continues to broaden its scope across the field of variants of uncertain significance classification.
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Macklin et al. (2020) conducted a case report in Extensive aortic, carotid, and abdominal dissections (n=1). Heterozygous deletion of exons 21-34 in MYLK was evaluated on Impact of deletion on protein function. A heterozygous deletion of exons 21-34 in MYLK in a patient with extensive dissections resulted in a loss of protein function due to the lack of any kinase domain.
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