Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
권호 표지
DOI QR코드

DOI QR Code

Novel Association of a Familial TGFBR1 Mutation in Loeys-Dietz Syndrome with Concomitant Hematologic Malignancy

  • Disha, Kushtrim (Department of Cardiac Surgery, Central Hospital Bad Berka) ;
  • Schulz, Solveig (Center of Human Genetics and Anthropology, Jena University Hospital) ;
  • Breuer, Martin (Department of Cardiac Surgery, Central Hospital Bad Berka) ;
  • Owais, Tamer (Department of Cardiac Surgery, Central Hospital Bad Berka) ;
  • Girdauskas, Evaldas (Department of Cardiovascular Surgery, University Heart Center Hamburg) ;
  • Kuntze, Thomas (Department of Cardiac Surgery, Central Hospital Bad Berka)
  • Received : 2019.03.12
  • Accepted : 2019.08.28
  • Published : 2019.10.05
Download PDF
⟨ Previous Next ⟩

Abstract

Concomitant Loeys-Dietz syndrome (LDS) and hematologic malignancies are exceptionally rare. This is the first report of a patient operated on for aortic root dilation who had been previously diagnosed with LDS and B-cell-lymphoma. After completion of chemotherapy and complete remission, an elective valve-sparing aortic root replacement (using the David-V method) was performed. Due to the positive family history, preoperative genetic counseling was conducted, and revealed LDS with a TGFBR1 (transforming growth factor beta receptor type I) mutation in 6 probands of the family, albeit in 1 of them posthumously. This missense mutation has been previously described in relation to aortic dissection, but a causative relationship to malignancy has so far neither been proposed nor proven.

Keywords

References

  1. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006;355:788-98. https://doi.org/10.1056/NEJMoa055695
  2. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet 2005;37:275-81. https://doi.org/10.1038/ng1511
  3. MacCarrick G, Black JH 3rd, Bowdin S, et al. Loeys-Dietz syndrome: a primer for diagnosis and management. Genet Med 2014;16:576-87. https://doi.org/10.1038/gim.2014.11
  4. Oderich GS, Panneton JM, Bower TC, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg 2005;42:98-106. https://doi.org/10.1016/j.jvs.2005.03.053
  5. Singh KK, Rommel K, Mishra A, et al. TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome. Hum Mutat 2006;27:770-7. https://doi.org/10.1002/humu.20354
  6. Akhurst RJ, Derynck R. TGF-beta signaling in cancer: a double-edged sword. Trends Cell Biol 2001;11:S44-51. https://doi.org/10.1016/S0962-8924(01)02130-4
  7. Bakkebo M, Huse K, Hilden VI, Smeland EB, Oksvold MP. TGF-$\beta$-induced growth inhibition in B-cell lymphoma correlates with Smad1/5 signalling and constitutively active p38 MAPK. BMC Immunol 2010;11:57. https://doi.org/10.1186/1471-2172-11-57
  8. Wang YQ, Qi XW, Wang F, Jiang J, Guo QN. Association between TGFBR1 polymorphisms and cancer risk: a metaanalysis of 35 case-control studies. PLoS One 2012;7:e42899. https://doi.org/10.1371/journal.pone.0042899