Thoracic aortic aneurysm or dissection

Gene: FBLN5

Red List (low evidence)

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

5 reviews

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

21 Feb 2019, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to FBLN5.

19 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

19 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Caroline Wright (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

19 Feb 2016, Gel status: 0

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

Mode of inheritance for FBLN5 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Feb 2016, Gel status: 0

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

Mode of inheritance for FBLN5 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

3 Jul 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

FBLN5 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Expert list