ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
17701892 Faivre et al. (2007) report on 1,013 patients with Marfan Syndrome or another fibrillinopathy and a pathogenic FBN1 mutation as part of the Universal Mutation Database for FBN1. There are 170 frameshift mutations and 137 nonsense mutations in this group.
30286810 Yang et al. (2018) performed MLPA on 115 unrelated patients with suspected Marfan or early onset aortic aneurysm/dissection were evaluated for deletions and duplications of FBN1 and TGFBR2. The authors identified 5 patients with single or multi exon deletions within the FBN1 gene. All 5 patients had multisystem deformities. Three patients were diagnosed with Classic Marfan syndrome. The additional 2 patients were eventually diagnosed with Marfan based on added criteria. No gross deleteions or duplication were identified in patients with only aortic aneurysm dissection without systemic involvement . The author suggests that gross deletions of FBN1 leads to Classic Marfan.
21063442 Hilhorst-Hofstee et al. (2011) report 5 patients from 1 family with a deletion that included the entire FBN1 gene. All deletion carriers had a diagnosis of Marfans based on the Ghent criteria for Marfan syndrome. The grandmother in this family was found to be mosaic based on the intensity of signals in both the MLPA and SNP analysis and was asymptomatic . The grandmother's results suggest a mosaic deletion.

Haploinsufficiency phenotype comments:

In summary, Loss of function variants (exonic deletions and whole gene deletions) of the FBN1 gene have been described in individuals with Marfan phenotype. Additional PMIDs: 21936929, 30479897, 17492313, 28842177 GeneReviews: Dietz H. Marfan Syndrome. 2001 Apr 18 [Updated 2017 Oct 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews? [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from:

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity