Thoracic aortic aneurysm or dissection

Gene: FBN1

Green List (high evidence)

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

7 reviews

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

Green List (high evidence)

Well characterised aortopathy gene; present on Wessex aortopathy and TAAD panels.
Created: 8 May 2019, 12:31 p.m.

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
  • South West GLH
  • London South GLH
  • North West GLH
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Expert list
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Ectopia lentis, familial (129600)
  • Marfan syndrome (154700)
  • Marfan lipodystrophy syndrome (616914)
  • Aortic aneurysm, ascending, and dissection
  • Weill-Marchesani syndrome 2, dominant, (608328)
  • Acromicric dysplasia (102370)
  • Stiff skin syndrome (184900)
  • MASS syndrome (604308)
  • ongenital contracturalarachnodactyly
  • Geleophysic dysplasia 2 (614185)
  • Marfan Syndrome
OMIM
134797
Clinvar variants
Variants in FBN1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to FBN1. Mode of inheritance for gene FBN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to FBN1.

14 Feb 2019, Gel status: 3

Added New Source, Set Phenotypes, Set publications, Status Update

Ellen McDonagh (Genomics England Curator)

Source North West GLH was added to FBN1. Added phenotypes Ectopia lentis, familial (129600); Marfan syndrome (154700); Marfan lipodystrophy syndrome (616914); Weill-Marchesani syndrome 2, dominant, (608328); Acromicric dysplasia (102370); Stiff skin syndrome (184900); MASS syndrome (604308); Geleophysic dysplasia 2 (614185) for gene: FBN1 Publications for gene FBN1 were changed from to 20082464 Rating Changed from Green List (high evidence) to Green List (high evidence)

19 Feb 2016, Gel status: 4

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

12 Aug 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

FBN1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Eligibility statement prior genetic testing

3 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene FBN1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

FBN1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,UKGTN,Expert list

3 Jul 2015, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene FBN1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

FBN1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,UKGTN,Expert list

3 Jul 2015, Gel status: 3

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene FBN1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

FBN1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,UKGTN,Expert list

3 Jul 2015, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene FBN1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

3 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

FBN1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,UKGTN,Expert list

3 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

FBN1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory,UKGTN,Expert list