title: A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description.
abstract: Mutations in MYLK cause non-syndromic familial thoracic aortic aneurysms and dissections (FTAAD). Very little is known about the phenotype of affected families. We sought to characterize the aortic disease and the presence of other vascular abnormalities in FTAAD caused by a deletion in MYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.
  
  
  
  We studied FTAAD in a 5-generation family that included 19 living members. Exome sequencing was performed to identify the underlying gene defect. Aortic elastic properties measured by TTE, MRI and pulse wave velocity were then compared between mutation carriers and non-carriers.
  
  
  
  Exome sequencing led to the identification of a 2-bp deletion in MYLK (c3272_3273del, p.Ser1091*) that led to a premature stop codon and nonsense-mediated decay. Eleven people were mutation carriers and eight people were non-carriers. Five aortic ruptures or dissections occurred in this family, with two survivors. There were no differences in aortic diameter or stiffness between carriers and non-carriers of the mutation.
  
  
  
  Individuals carrying this deletion in MYLK have a high risk of presenting with an acute aortic dissection or rupture. Aortic events occur over a wide range of ages and are not always preceded by obvious aortic dilatation. Aortic elastic properties do not differ between carriers and non-carriers of this mutation, rendering it uncertain whether and when carriers should undergo elective prophylactic surgery.
authors: Department of Surgical and Perioperative Sciences, Heart Centre, Umeå University, 901 85, Umeå, Sweden. matias.hannuksela@umu.se.
authors: Matias
authors: M
authors: Hannuksela
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.|Department of Medical Biosciences, Medical and Clinical Genetics, Umeå University, Umeå, Sweden.
authors: Eva-Lena
authors: EL
authors: Stattin
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Joakim
authors: J
authors: Klar
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors: Adam
authors: A
authors: Ameur
authors: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Bengt
authors: B
authors: Johansson
authors: Department of Radiation Sciences, Umeå University Hospital, Umeå, Sweden.
authors: Karen
authors: K
authors: Sörensen
authors: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors: Bo
authors: B
authors: Carlberg
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000000981:diagnostic imaging; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D063177:Pulse Wave Analysis; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D002135:Calcium-Binding Proteins; D004247:DNA; C499378:MYLK protein, human; D009219:Myosin-Light-Chain Kinase
keywords: Aortic dissection; Gene mutation; MYLK; Thoracic aorta