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Start Over Author "Johnston, Tami" Topic calcium-binding proteins
2 results on '"Johnston, Tami"'

1. MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants.

Author

Wallace SE, Regalado ES, Gong L, Janda AL, Guo DC, Russo CF, Kulmacz RJ, Hanna N, Jondeau G, Boileau C, Arnaud P, Lee K, Leal SM, Hannuksela M, Carlberg B, Johnston T, Antolik C, Hostetler EM, Colombo R, and Milewicz DM

Subjects
Adult, Aged, Aortic Dissection, Aorta pathology, Aorta surgery, Aortic Diseases pathology, Aortic Diseases surgery, Female, Heterozygote, Humans, Male, Middle Aged, Pedigree, Pregnancy, Aortic Diseases genetics, Calcium-Binding Proteins genetics, Genetic Testing, High-Throughput Nucleotide Sequencing, Myosin-Light-Chain Kinase genetics
Abstract

Purpose: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense 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 MYLK pathogenic 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.

Published
2019
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2. MYLK Mutations: Aortic Disease Presentation, Pregnancy Risk, and Characterization of Pathogenic Missense Variants

Author

Wallace, Stephanie E., Regalado, Ellen S., Gong, Limin, Janda, Alexandra L., Guo, Dong-chuan, Russo, Claudio F., Kulmacz, Richard J., Hanna, Nadine, Jondeau, Guillaume, Boileau, Catherine, Arnaud, Pauline, Lee, Kwanghyuk, Leal, Suzanne M., Hannuksela, Matias, Carlberg, Bo, Johnston, Tami, Antolik, Christian, Hostetler, Ellen M., Colombo, Roberto, and Milewicz, Dianna M.

Subjects
Adult, Male, Heterozygote, MYLK, acute aortic dissection, Calcium-Binding Proteins, Aortic Diseases, High-Throughput Nucleotide Sequencing, Middle Aged, thoracic aortic surgery, Article, Pedigree, Aortic Dissection, myosin light chain kinase, Pregnancy, cardiovascular system, Humans, Female, Genetic Testing, hereditary thoracic aortic disease, Myosin-Light-Chain Kinase, Aorta, Aged
Abstract

Purpose Heritable thoracic aortic disease (HTAD) can result from null variants in MYLK, which encodes myosin light chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. Methods Clinical data from 33 cases with MYLK pathogenic variants were analyzed (5 null and 2 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 were aortic dissections (87%). Aortic diameters were minimally enlarged at the time of dissection in many cases. Time to aortic event curves showed missense mutation carriers have earlier onset aortic events than null mutation carriers. A MYLK missense variant segregated with aortic disease over five generations but only marginally decreases MLCK kinase activity, and functional assays fail to identify all pathogenic variants in MYLK. Conclusions These data further define aortic phenotype associated with MYLK pathogenic variants. Given minimal aortic enlargement prior to dissection, an alternative approach to guide the timing of aortic repair is proposed based the probability of a dissection at a given age.

Published
2018

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