Thoracic aortic aneurysm and dissection

Gene: FBN2

Green List (high evidence)

FBN2 (fibrillin 2)
EnsemblGeneIds (GRCh38): ENSG00000138829
EnsemblGeneIds (GRCh37): ENSG00000138829
OMIM: 612570, Gene2Phenotype
FBN2 is in 10 panels

9 reviews

James Eden (Manchester)

Green List (high evidence)

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

Phenotypes
Contractural arachnodactyly, congenital 121050; Macular degeneration, early-onset 616118

Publications

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

Green List (high evidence)

On CGGL Royal Brompton panel. Phenotypic overlap with MFS, although weaker association with aortic dissection/aneurysm, but some good evidence (PMID: 19006240; 25944730, although FBN2 variants in this paper were VUS). Appropriate for inclusion based on phenotypic overlaps.
Created: 18 Sep 2019, 2:26 p.m. | Last Modified: 18 Sep 2019, 2:26 p.m.
Panel Version: 0.30

Phenotypes
Congenital contractural arachnodactyly

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

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
Comment on list classification: Promoted from amber to green based on expert reviews.
Created: 17 Sep 2019, 8:19 a.m. | Last Modified: 17 Sep 2019, 8:19 a.m.
Panel Version: 0.30

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

Green List (high evidence)

Present on Wessex aortopathy panel.
Associated with congenital contractural arachnodactyly (OMIM #121050), which has significant phenotypic overlap with Marfan syndrome.
Created: 29 Aug 2019, 2:07 p.m. | Last Modified: 29 Aug 2019, 2:07 p.m.
Panel Version: 0.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital contractural arachnodactyly

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

Rebecca Whittington (South West GLH)

Green List (high evidence)

121050 Contractural arachnodactyly - CTD including aortic root dilatation, patent ductus arteriosus, BAV, VSD, ASD, mitral valve prolapse and mitral regurgitation
Created: 25 Mar 2019, 4:30 p.m.
Wooderchak-Donahue et al 2015 Am J Med Genet A 167A:1747 PMID:25944730 5 missense variants identified in Marfan/Marfan-like cohort: 3302A>G Asn1101Ser, 3793G>A Glu1265Lys, 4454A>G Asp1485Gly, 4657C>T Arg1553Cys, 5627G>C Cys1876Ser - all reported as VUS. Callewaert et al 2009 Hum Mutat 30:334 PMID:19006240 review FBN2 variants in contractural arachnodactyly and comment on involvement of aortopathy in phenotype of more recently described cases.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

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.
Not on the Inherited Cardiac Condition Genes panel for familial aortic anuerysm, 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.
Created: 19 Feb 2016, 10:49 a.m.

Matina Prapa (Genomics England Curator)

I don't know

Strong association with contractural arachnodactyly. However, in the context of familial thoracic aortic aneurysm, evidence is much weaker with only a single case report complicated with Aortic Dilatation and Dissection (see PMID above) and other weak association with progressive aortic dilatation (ref within above case report).
Created: 9 Feb 2016, 3:38 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
#121050 - Contractural arachnodactyly, congenital; #616118- Macular degeneration, early-onset

Publications

David Parry (University of Edinburgh)

I don't know

Reported dilatations are infrequent and relatively mild. No reported dissections associated with FBN2 mutations to date. Although strong evidence for causation of CCA and associated defects, evidence for involvement in FTAAD is less clear.
Created: 13 Nov 2015, 4:31 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • South West GLH
  • London South GLH
  • South West GLH
  • London South GLH
Phenotypes
  • Congenital Contractural Arachnodactyly
  • Contractural arachnodactyly, congenital, 121050
OMIM
612570
Clinvar variants
Variants in FBN2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

19 Nov 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: FBN2 were set to

17 Sep 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: fbn2 has been classified as Green List (High Evidence).

18 Apr 2019, Gel status: 2

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

Ellen McDonagh (Genomics England Curator)

gene: FBN2 was added gene: FBN2 was added to GMS FTAAD placeholder panel. Sources: Expert Review Amber,London South GLH,South West GLH Mode of inheritance for gene: FBN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FBN2 were set to Congenital Contractural Arachnodactyly; Contractural arachnodactyly, congenital, 121050