Thoracic aortic aneurysm and dissection

Gene: FBLN5

Green List (high evidence)

FBLN5 (fibulin 5)
EnsemblGeneIds (GRCh38): ENSG00000140092
EnsemblGeneIds (GRCh37): ENSG00000140092
OMIM: 604580, Gene2Phenotype
FBLN5 is in 12 panels

8 reviews

Kate Thomson (Oxford University Hospitals Foundation Trust)

Green List (high evidence)

Submitted on behalf of the GMS Cardiology specialist group. This gene did not achieve a consensus Green rating; however, the group agreed that the existing evidence (published and in-house data) was sufficient to support inclusion in this panel.
Created: 9 Dec 2019, 1:19 p.m. | Last Modified: 9 Dec 2019, 1:19 p.m.
Panel Version: 0.55

Ivone Leong (Genomics England Curator)

I don't know

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

James Eden (Manchester)

I don't know

Gene is associated with cutis laxa, which includes aortic symptoms. Also associated with age-related macular degeneration and autistic spectrum disorder in HGMD.
Created: 2 Oct 2019, 12:27 p.m. | Last Modified: 2 Oct 2019, 12:28 p.m.
Panel Version: 0.32

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
?Cutis laxa, autosomal dominant 2 614434; Cutis laxa, autosomal recessive, type IA 219100; Macular degeneration, age-related, 3 608895; Neuropathy, hereditary, with or without age-related macular degeneration 608895

Publications

Rebecca Whittington (South West GLH)

Green List (high evidence)

614434/219100 AD/AR Cutis Laxa - cardiac phenotype includes ascending aortic aneurysm, vascular tortuosity and SVAS. Most HGMD variants (10) are associated with age-related macular degeneration, but 7 variants reported in association with cutis laxa
Created: 25 Mar 2019, 4:30 p.m.
Callewaert et al 2013 Hum Mutat 34:111 PMID:22829427 describe one missense and one nonsense variant c.649T>C p.Cys217Arg; c.1171G>T p.Glu391X (both homozygous in consanguineous families) but do not report segregation or functional analysis for either variant, but both had significant family history; p.Cys217Arg has previously been reported elsewhere. Hu et al 2006 Hum Mol Genet 15:3379 PMID:17035250 carried out functional analysis on two missense variants including Cys217Arg and have shown fibulin-5 is absent in skin from a homozygous p.ser227Pro patient with resulting disorganisation of elastic fibres. Loeys et al 2002 11:2113 PMID:12189163 characterised the Ser224Pro variant in 4 homozygous affected members of a large consangineous family - segregation data.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Nick Camm (NHS)

Green List (high evidence)

Caroline Wright (Genomics England Curator)

Comment when marking as ready: Unclear cause of TAAD
Created: 19 Feb 2016, 3:22 p.m.
Comment on mode of inheritance: Both observed on OMIM and in literature
Created: 19 Feb 2016, 3:22 p.m.

Ellen McDonagh (Genomics England Curator)

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, 10:57 a.m.

Matina Prapa (Genomics England Curator)

I don't know

Fibulin-5 knockout mice have been demonstrated to have tortuosity and elongation of the aorta, particularly in the ascending aorta (PMID: 11805835; 11805834). Also, decreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissection (PMID: 16153447). However, no polymorphisms have been linked to TAAD and haplotype analysis in AAA revealed no correlations with FBLN5 genetic variation (PMID: 20133342).
Created: 12 Feb 2016, 4:25 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
#614434- Cutis laxa, autosomal dominant 2; #219100- Cutis laxa, autosomal recessive, type IA

Publications

History Filter Activity

9 Dec 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to FBLN5. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

18 Nov 2019, Gel status: 2

Added New Source, Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to FBLN5. Source Expert Review Amber was added to FBLN5. Rating Changed from Red List (low evidence) to Amber List (moderate evidence)

18 Nov 2019, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: FBLN5 were set to

18 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

gene: FBLN5 was added gene: FBLN5 was added to GMS FTAAD placeholder panel. Sources: South West GLH,Expert Review Red Mode of inheritance for gene: FBLN5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal