umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants
Show others and affiliations
2019 (English)In: Genetics in Medicine, ISSN 1098-3600, E-ISSN 1530-0366, Vol. 21, no 1, p. 144-151Article in journal (Refereed) Published
Abstract [en]

Purpose: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLKmissense variants are pathogenic and information to guide aortic disease management are limited.

Methods: Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed.

Results: Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK.

Conclusion: These data further define the aortic phenotype associated with MYLKpathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 21, no 1, p. 144-151
Keywords [en]
acute aortic dissection, hereditary thoracic aortic disease, MYLK, myosin light-chain kinase, thoracic aortic surgery
National Category
Genetics
Identifiers
URN: urn:nbn:se:umu:diva-155775DOI: 10.1038/s41436-018-0038-0ISI: 000455403400020PubMedID: 29925964OAI: oai:DiVA.org:umu-155775DiVA, id: diva2:1283090
Funder
NIH (National Institute of Health), RO1 HL109942NIH (National Institute of Health), P01HL110869-01Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Hannuksela, MatiasCarlberg, Bo

Search in DiVA

By author/editor
Arnaud, PaulineLee, KwanghyukHannuksela, MatiasCarlberg, Bo
By organisation
Department of Surgical and Perioperative SciencesDepartment of Public Health and Clinical Medicine
In the same journal
Genetics in Medicine
Genetics

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 38 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf