A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Hannuksela, Matias; Stattin, Eva-Lena; Klar, Joakim; Ameur, Adam; Johansson, Bengt; Sörensen, Karen; Carlberg, Bo
• Is Part Of: BMC medical genetics. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-12
• Subjects: Thoracic aorta -- Aortic dissection -- Gene mutation -- MYLK; Medical genetics -- Periodicals; 616.04205
• DOI: 10.1186/s12881-016-0326-y
• Languages: English
• ISSNs: 1471-2350

Abstract

Abstract Background Mutations inMYLK 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 inMYLK and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers. Methods 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. Results Exome sequencing led to the identification of a 2-bp deletion inMYLK (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. Conclusions Individuals carrying this deletion inMYLK 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.