Familial aortic disease and a large duplication in chromosome 16p13.1

• Verfasst von: Erhart, Philipp [VerfasserIn]
• Verfasst von: Straub, Beate Katharina [VerfasserIn]
• Verfasst von: Haußer-Siller, Ingrid [VerfasserIn]
• Verfasst von: Böckler, Dittmar [VerfasserIn]
• Verfasst von: Grond-Ginsbach, Caspar [VerfasserIn]
• Titel: Familial aortic disease and a large duplication in chromosome 16p13.1
• Verf.angabe: Philipp Erhart, Tobias Brandt, Beate K. Straub, Ingrid Hausser, Sabine Hentze, Dittmar Böckler, Caspar Grond-Ginsbach
• E-Jahr: 2018
• Jahr: 14 February 2018
• Umfang: 5 S.
• Fussnoten: Gesehen am 20.04.2018
• Titel Quelle: Enthalten in: Molecular genetics & genomic medicine
• Ort Quelle: Chichester [u.a.] : Wiley, 2013
• Jahr Quelle: 2018
• Band/Heft Quelle: 6(2018), 3, Seite 441-445
• ISSN Quelle: 2324-9269
• DOI: doi:10.1002/mgg3.371
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: cosegregation
• Sach-SW: duplication 16p13.1
• Sach-SW: familial thoracic aortic aneurysm and dissection
• Sach-SW: whole exome sequencing
• K10plus-PPN: 1572209062
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Background and purpose A recurrent duplication of chromosome 16p13.1 was associated with aortic dissection as well as with cervical artery dissection. We explore the segregation of this duplication in a family with familial aortic disease. Methods Whole exome sequencing (WES) analysis was performed in a patient with a family history of aortic diseases and ischemic stroke due to an aortic dissection extending into both carotid arteries. Results The index patient, his affected father, and an affected sister of his father carried a large duplication of region 16p13.1, which was also verified by quantitative PCR. The duplication was also found in clinically asymptomatic sister of the index patient. WES did not detect pathogenic variants in a predefined panel of 11 genes associated with aortic disease, but identified rare deleterious variants in 14 genes that cosegregated with the aortic phenotype. Conclusions The cosegregation of duplication 16p13.1 with the aortic phenotype in this family suggested a causal relationship between the duplication and aortic disease. Variants in known candidate genes were excluded as disease-causing in this family, but cosegregating variants in other genes might modify the contribution of duplication 16p13.1 on aortic disease.