Advertisement

Hereditary thoracic aortic disease associated with cysteine substitution c.937T > G p.(Cys313Gly) in FBN1

  • E. OverwaterEmail author
  • K. Van Rossum
  • M. J. H. Baars
  • A. Maugeri
  • A. C. Houweling
Open Access
Heart Beat
A 56-year-old male was diagnosed with a type A aortic dissection, followed by a type B dissection 3 years later. There were no other signs indicating a familial connective tissue disorder. Pathogenic variant c.937T > G p.(Cys313Gly) in FBN1 [(NM_000138.4), Online Mendelian Inheritance in Man (OMIM) entry *134797] was identified by DNA testing, consistent with Marfan syndrome (OMIM entry #154700). The variant was identified in 21 out of 53 tested relatives (Fig. 1). A thoracic aortic aneurysm was diagnosed in eight relatives carrying the variant, three of whom met the criteria for preventive surgery. One of the deceased obligate carriers probably had a thoracic aortic aneurysm. Most mutation carriers had a systemic score [1] of zero or one, although the highest score was four. As illustrated by this image, FBN1 variant c.937T > G p.(Cys313Gly) can cause isolated aortic disease. Timely recognition of individuals with a pathogenic FBN1 variant is highly important, as it enables the prevention of severe cardiovascular complications [2, 3].
Fig. 1

Pedigree depicting thoracic aortic aneurysms and/or dissections. Squares represent males, circles indicate females

Notes

Conflict of interest

E. Overwater, K. Van Rossum, M.J.H. Baars, A. Maugeri and A.C. Houweling declare that they have no competing interests.

Ethical standards

Written informed consent for publication was obtained from all the carriers of FBN1 variant c.937T > G p.(Cys313Gly).

References

  1. 1.
    Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–85.CrossRefGoogle Scholar
  2. 2.
    Regalado ES, Guo DC, Santos-Cortez RL, Hostetler E, Bensend TA, Pannu H, et al. Pathogenic FBN1 variants in familial thoracic aortic aneurysms and dissections. Clin Genet. 2016;89(6):719–23.CrossRefGoogle Scholar
  3. 3.
    Rurali E, Perrucci GL, Pilato CA, Pini A, Gaetano R, Nigro P, et al. Precise therapy for thoracic aortic aneurysm in Marfan syndrome: a puzzle nearing its solution. Prog Cardiovasc Dis. 2018;61(3–4:328–35.CrossRefGoogle Scholar

Copyright information

© The Author(s) 2019

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • E. Overwater
    • 1
    • 2
    Email author
  • K. Van Rossum
    • 2
  • M. J. H. Baars
    • 1
  • A. Maugeri
    • 2
  • A. C. Houweling
    • 2
  1. 1.Department of Clinical Genetics, Amsterdam UMCUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Clinical Genetics, Amsterdam UMCVrije Universiteit AmsterdamAmsterdamThe Netherlands

Personalised recommendations