Thoracic aortic aneurysm or dissection

Gene: EFEMP2

Green List (high evidence)

EFEMP2 (EGF containing fibulin extracellular matrix protein 2)
EnsemblGeneIds (GRCh38): ENSG00000172638
EnsemblGeneIds (GRCh37): ENSG00000172638
OMIM: 604633, Gene2Phenotype
EFEMP2 is in 7 panels

5 reviews

Rebecca Whittington (South West GLH)

Green List (high evidence)

614437 Cutis Laxa - CTD phenotype including aortic/pulmonory artery anuerysms and arterial/venous tortuosity, arterial stenosis and vascular fragility. Missense, splicing and frameshift variants
Created: 25 Mar 2019, 4:30 p.m.
Letard et al 2018 Mol Syndromol 9:190 PMID:30140196 report a severe cutis laxa phenotype in a terminated pregnancy homozygous for an EFEMP2 nonsense variant c.639C>A (p.Cys213*) and review/list previously reported EFEMP2 variants. 0.00041% gnomAD (AR association).
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Nick Camm (NHS)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

PMID:22440127 (2012) recruited 9 patients, from 4 unrelated consanguineous families, with recessively-inherited aortic aneurysm. ECG revealed a wide spectrum of severity of AA but skin manifestations of cutis laxa were not found in any patient. Sequence analysis of EFEMP2 identified a novel homozygous variend (p.E161K) in all 9 affected patients. This reference forms the basis for the ClinGen TAAD 'moderate' evidence assignment.
Created: 11 Oct 2017, 11:39 a.m.

Matina Prapa (Genomics England Curator)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#614437- Cutis laxa, autosomal recessive, type IB

Publications

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. One mutation is listed in this gene in supplemental table.
Created: 19 Feb 2016, 10:22 a.m.
PMID: 16685658 is a case report of a female with severe, recessive connective-tissue disease including cutis laxa, bone fragility, vascular tortuosity and aneurysm, developmental emphysema, and diaphragmatic and inguinal hernia. At age 2 years, she received a diagnosis of an aortic root aneurysm. Screening of FBLN4 revealed a homozygous missense mutation (169G>A; E57K) in the patient. Both parents were heterozygous.
Created: 1 Feb 2016, 11:58 a.m.
PMID: 17937443 is a case report of a female with compound heterozygous mutations c.835C > T (p.R279C)/c.1070_1073dupCCGC in fibulin 4 (EFEMP2), who died at 27 days of age. Autopsy examination of the patient showed apparently long hands, bronchopneumonia with focal alveolar damage, arterial wall thickening, acute renal tubular damage, biventricular hypertrophy and right ventricle dilatation, aneurysmal dilation of the ascending aorta and main branches of pulmonary arteries with dissection of the wall. There was intussusception-like telescoping of the inner arterial layer causing severe luminal narrowing of the main branches of the pulmonary arteries. The pregnancy was complicated by maternal cocaine abuse and tobacco smoking.
Created: 1 Feb 2016, 11:50 a.m.
Previously known as FBLN4.
Created: 1 Feb 2016, 11:34 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
PMID: 17937443; 16685658; 22440127

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • South West GLH
  • London South GLH
  • Expert Review Green
  • Expert list
Phenotypes
  • Cutis laxa, autosomal recessive, type IB, 614437
  • aortic aneurysm
OMIM
604633
Clinvar variants
Variants in EFEMP2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Feb 2019, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to EFEMP2.

20 Feb 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to EFEMP2. Rating Changed from Green List (high evidence) to Green List (high evidence)

11 Oct 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for EFEMP2 were set to Cutis laxa, autosomal recessive, type IB, 614437; aortic aneurysm

29 Jun 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for EFEMP2 were set to Cutis laxa, autosomal recessive, type IB, 614437

29 Jun 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for EFEMP2 were set to 20019329; 17937443; 22440127; 16685658

29 Jun 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for EFEMP2 were set to 20019329; 17937443

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).

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).

19 Feb 2016, Gel status: 0

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

Mode of inheritance for EFEMP2 was changed to BIALLELIC, autosomal or pseudoautosomal

3 Jul 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

EFEMP2 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Expert list