Thoracic aortic aneurysm and dissection

Gene: FBN1

Green List (high evidence)

FBN1 (fibrillin 1)
EnsemblGeneIds (GRCh38): ENSG00000166147
EnsemblGeneIds (GRCh37): ENSG00000166147
OMIM: 134797, Gene2Phenotype
FBN1 is in 16 panels

9 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.
Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Green List (high evidence)

On CGGL Royal Brompton panel. Multiple pathogenic variants reported. Cardinal gene for Marfan syndrome.
Created: 18 Sep 2019, 2:15 p.m. | Last Modified: 18 Sep 2019, 2:15 p.m.
Panel Version: 0.30

Phenotypes
Marfan syndrome

Variants in this GENE are reported as part of current diagnostic practice

Alison Callaway (Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust)

Green List (high evidence)

Well characterised gene (Marfan syndrome / aortopathy); present on Wessex aortopathy and TAAD panels.
Created: 29 Aug 2019, 2:31 p.m. | Last Modified: 29 Aug 2019, 2:31 p.m.
Panel Version: 0.5

Phenotypes
Marfan syndrome; Ectopia lentis

Variants in this GENE are reported as part of current diagnostic practice

Rebecca Whittington (South West GLH)

Green List (high evidence)

154700 Marfan syndrome; well characterised gene
Created: 25 Mar 2019, 4:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

James Eden (Manchester)

Green List (high evidence)

Gene currently tested on Manchester cardiac gene panel. 2721 variants listed on HGMD (accessed 29/01/2019). ClinGen Knowledge Base: definitive association with TAAD (accessed 29/01/2019).
Created: 14 Feb 2019, 1:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Acromicric dysplasia (102370); Ectopia lentis, familial (129600); Geleophysic dysplasia 2 (614185); Marfan lipodystrophy syndrome (616914); Marfan syndrome (154700); MASS syndrome (604308); Stiff skin syndrome (184900); Weill-Marchesani syndrome 2, dominant, (608328)

Publications

Variants in this GENE are reported as part of current diagnostic practice

David Parry (University of Edinburgh)

Green List (high evidence)

Nick Camm (NHS)

Green List (high evidence)

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.
On the Inherited Cardiac Condition Genes panel reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 24.
Created: 19 Feb 2016, 10:48 a.m.

Publications

  • 7762551
  • doi:10.​1007/​s12265-016-9673-5

Helen Savage (Congenica Ltd)

Green List (high evidence)

Mutations in exons 24-32 are associated with a more severe phenotype, often manifesting in the neonatal period.
Mutations in exons 41 and 42 also cause Acromicric dysplasia and Geleophysic dysplasia.
Created: 20 Jan 2016, 4:48 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Marfan syndrome; tall; Arachnodactyly; scoliosis; Aortic root dilatation; Aortic dissection; Pectus excavatum; hypermobile joints; pes planus; ectopia lentis

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • North West GLH
  • South West GLH
  • London South GLH
  • Expert Review Green
  • South West GLH
  • London South GLH
  • North West GLH
Phenotypes
  • Weill-Marchesani syndrome 2, dominant, (608328)
  • Marfan syndrome (154700)
  • Ectopia lentis, familial (129600)
  • Marfan lipodystrophy syndrome (616914)
  • MASS syndrome (604308)
  • Stiff skin syndrome (184900)
  • Geleophysic dysplasia 2 (614185)
  • Marfan Syndrome
  • Aortic aneurysm, ascending, and dissection
  • ongenital contracturalarachnodactyly
  • Acromicric dysplasia (102370)
OMIM
134797
Clinvar variants
Variants in FBN1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Sep 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: FBN1 were set to

18 Apr 2019, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Ellen McDonagh (Genomics England Curator)

gene: FBN1 was added gene: FBN1 was added to GMS FTAAD placeholder panel. Sources: Expert Review Green,London South GLH,South West GLH,North West GLH Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FBN1 were set to Weill-Marchesani syndrome 2, dominant, (608328); Marfan syndrome (154700); Ectopia lentis, familial (129600); Marfan lipodystrophy syndrome (616914); MASS syndrome (604308); Stiff skin syndrome (184900); Geleophysic dysplasia 2 (614185); Marfan Syndrome; Aortic aneurysm, ascending, and dissection; ongenital contracturalarachnodactyly; Acromicric dysplasia (102370)