The spectrum of FBN1, TGFβR1, TGFβR2 and ACTA2 variants in 594 individuals with suspected Marfan Syndrome, Loeys-Dietz Syndrome or Thoracic Aortic Aneurysms and Dissections (TAAD)

Mol Genet Metab. 2014 Jun;112(2):171-6. doi: 10.1016/j.ymgme.2014.03.011. Epub 2014 Apr 2.

Abstract

Introduction: In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and Dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGFβR1, TGFβR2 and ACTA2 genes.

Methods: We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGFβR1, TGFβR2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions.

Results: A total of 112 patients had a positive result. Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; of these, 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel.

Conclusion: This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD.

Keywords: Aortic aneurysms; FBN1; Loeys–Dietz Syndrome; Marfan Syndrome; Thoracic Aortic Aneurysms and Dissections.

MeSH terms

  • Actins / genetics*
  • Adolescent
  • Adult
  • Aged
  • Aortic Aneurysm / diagnosis*
  • Aortic Aneurysm / genetics
  • Aortic Aneurysm / pathology
  • Child
  • Child, Preschool
  • Female
  • Fibrillin-1
  • Fibrillins
  • Genetic Testing
  • Genetic Variation*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Marfan Syndrome / diagnosis*
  • Marfan Syndrome / genetics
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Mutation
  • Receptors, Transforming Growth Factor beta / genetics*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • ACTA2 protein, human
  • Actins
  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins
  • Receptors, Transforming Growth Factor beta