Thoracic aortic aneurysm and dissection

Gene: BGN

Green List (high evidence)

BGN (biglycan)
EnsemblGeneIds (GRCh38): ENSG00000182492
EnsemblGeneIds (GRCh37): ENSG00000182492
OMIM: 301870, Gene2Phenotype
BGN is in 8 panels

6 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. Therefore this gene has been promoted from Amber to Green
Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35
Comment on mode of inheritance: MOI has been corrected.
Created: 2 Oct 2019, 11:55 a.m. | Last Modified: 2 Oct 2019, 11:55 a.m.
Panel Version: 0.31

James Eden (Manchester)

Green List (high evidence)

Gene not currently tested on Manchester cardiac gene panel. 9 variants listed on HGMD (accessed 24/09/2019). ClinGen Knowledge Base: limited association with familial TAAD (accessed 24/09/2019). Literature is convincing for association with TAAD.
Created: 25 Sep 2019, 9:09 a.m. | Last Modified: 25 Sep 2019, 9:09 a.m.
Panel Version: 0.30

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Meester-Loeys syndrome, 300989; Spondyloepimetaphyseal dysplasia, X-linked, 300106

Publications

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

Green List (high evidence)

On CGGL Royal Brompton FTAAD panel. Only VUS reported so far, but strong association with syndromic FTAAD, therefore good evidence for inclusion here.
Created: 18 Sep 2019, 3:06 p.m. | Last Modified: 18 Sep 2019, 3:06 p.m.
Panel Version: 0.30

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
OMIM: 300989 Meester-Loeys syndrome

Publications

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

Rebecca Whittington (South West GLH)

Green List (high evidence)

300989 Meester-Loeys syndrome; phenotype includes aortic aneurysm and dissection as well as rare pulmonory and cerebral artery aneurysm in addition to other syndromic connective tissue phenotypes; female carriers variable phenotype from unaffected to fatal aortic dissection (OMIM).
Created: 25 Mar 2019, 4:30 p.m.
Meester et al 2017 Genet Med 19:386 PMID:27632686 report one nonsense, two missense and two large deletions affecting multiple exons of BGN but no additional genes. Nonsense variant c.5G>A, p.Trp2* with no gnomAD freq, seg in two affected family members and 2 ClinVar submissions as pathogenic. Missense variants c.908A>C, p.Gln303Pro and c.238G>A,p.Gly80Ser both with no gnomAD freq and 2 ClinVar submissions as pathogenic.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

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.

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked BGN as ready: July 4th 2017.
Created: 4 Jul 2017, 3:11 p.m.
Comment on mode of inheritance: X-linked MOI supported by PMID:27632686 and curation notes in the ClinGen TAAD panel (https://search.clinicalgenome.org/kb/gene-validity/8260).
Created: 4 Jul 2017, 3:11 p.m.
Comment on list classification: Updated rating from Red to Green: Green rating approved by Helen Brittain: >3 unrelated cases supporting causation for syndromic TAAD in PMID:27632686, plus mouse model in PMID:17502576. The only reason BGN is not given 'Strong' evidence on the ClinGen TAAD panel (see https://search.clinicalgenome.org/kb/gene-validity), is because the ClinGen panel focuses on isolated TAAD; notes on the ClinGen panel support involvement of BGN in syndromic TAAD.
Created: 4 Jul 2017, 3:04 p.m.
Mouse model in PMID:17502576: the spontaneous death of biglycan-deficient male mice from aortic rupture implicates biglycan as essential for the structural and functional integrity of the aortic wall and suggests a potential role of biglycan gene defects in the pathogenesis of aortic dissection and rupture in humans.
Created: 29 Jun 2017, 12:47 p.m.
Present on the ClinGen 'Familial thoracic aortic aneurysm and aortic dissection' gene panel with the summary: Strong [evidence] for syndromic , X-linked TAAD and “limited” [evidence] for isolated TAAD.There was 1 reported proband with isolated TAAD harboring variant in this gene.
Created: 29 Jun 2017, 12:45 p.m.
PMID:27632686 (2017) show that LOF mutations in BGN cause a syndromic form of thoracic aortic aneurysms and dissection (TAAD). They sequenced 368 candidate genes in 11 Marfan probands without a genetic diagnosis, and found 2 unrelated individuals with BGN mutations (p.Trp2* and p.Gln303Pro). Subsequent sequencing of BGN in 360 male and 155 females unexplained TAAD probands identified further cases (5 individuals in total).
Created: 29 Jun 2017, 12:43 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
syndromic thoracic aortic aneurysm and dissection; X-linked syndromic TAAD

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • NHS GMS
  • Expert Review Green
  • South West GLH
  • London South GLH
  • South West GLH
  • London South GLH
Phenotypes
  • X-linked syndromic TAAD
  • syndromic thoracic aortic aneurysm and dissection
OMIM
301870
Clinvar variants
Variants in BGN
Penetrance
None
Panels with this gene

History Filter Activity

18 Nov 2019, Gel status: 3

Added New Source, Added New Source, Status Update

Ivone Leong (Genomics England Curator)

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

2 Oct 2019, Gel status: 2

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: BGN was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

18 Apr 2019, Gel status: 2

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

Ellen McDonagh (Genomics England Curator)

gene: BGN was added gene: BGN was added to GMS FTAAD placeholder panel. Sources: Expert Review Amber,London South GLH,South West GLH Mode of inheritance for gene: BGN was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: BGN were set to X-linked syndromic TAAD; syndromic thoracic aortic aneurysm and dissection