Thoracic aortic aneurysm or dissection

Gene: FLNA

Green List (high evidence)

FLNA (filamin A)
EnsemblGeneIds (GRCh38): ENSG00000196924
EnsemblGeneIds (GRCh37): ENSG00000196924
OMIM: 300017, Gene2Phenotype
FLNA is in 26 panels

6 reviews

Ivone Leong (Genomics England Curator)

Comment on mode of inheritance: MOI was corrected.
Created: 30 Sep 2019, 10:51 a.m. | Last Modified: 30 Sep 2019, 10:51 a.m.
Panel Version: 1.97

Rebecca Whittington (South West GLH)

Green List (high evidence)

314400 Cardiac valvular dysplasia, X-linked; 300048 Congenital short bowel syndrome; 309350 Melnick-Needles syndrome all have aortic involvement
Created: 25 Mar 2019, 4:30 p.m.
Chen et al 2018 Am J Med Genet A 176:337 PMID:29334594 examine patients with FLNA for cardiac features and found that 18% had thoracic aortic aneurysm/dilation and 57% had other cardiac abnormalites. This included two patients who died of aortic rupture at aortic diameters smaller than that reccomended for surgery in other aortopathies.
Created: 25 Mar 2019, 4:27 p.m.

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

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

Nick Camm (NHS)

Green List (high evidence)

Rebecca Foulger (Genomics England curator)

Comment on phenotypes: TAAD phenotype taken from Emory sequencing panel.
Created: 29 Jun 2017, noon
FLNA is associated with a syndromic form of TAAD, namely the periventricular nodular heterotopia type 1 (PVNH1; also known as the Ehlers-Danlos variant of PVNH, MIM:300049). FLNA is confirmed DD-G2P gene for MIM:300049, though FLNA only explains a small number of the X-linked TAAD families.
Created: 29 Jun 2017, 11:58 a.m.

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, 10:57 a.m.

Matina Prapa (Genomics England Curator)

Green List (high evidence)

FLNA mutations initially associated with periventricular nodular heterotopias (OMIM 300049). More recently, patients with mitral valve disease, aortic root dilatation, and joint hypermobility without periventricular nodular heterotopias have been associated with FLNA mutations (see ref above, also: http://www.ashg.org/2013meeting/abstracts/fulltext/f130120800.htm)

Mode of inheritance: FLNA heterozygous female mice had variable clinical features of less severity compared to FLNA-Null mice with features suggesting vascular remodelling failure (coarse and dilated vasculature, haemorrhage and oedema)- PMID: 17172441

Created: 14 Feb 2016, 11:56 a.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
300537- Heterotopia, periventricular, ED variant; 300049- Heterotopia, periventricular; 314400- Cardiac valvular dysplasia, X-linked

Publications

History Filter Activity

30 Sep 2019, Gel status: 3

Set mode of inheritance

Ivone Leong (Genomics England Curator)

Mode of inheritance for gene: FLNA 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)

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

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

20 Feb 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

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

29 Jun 2017, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FLNA were set to Marfan Syndrome, Thoracic Aortic Aneurysm & Dissection (TAAD), and Related Disorders

29 Jun 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FLNA were set to 23032111; 26188975; 17172441

26 Jun 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FLNA were set to 23032111

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

Set Mode of Inheritance

Caroline Wright (Genomics England Curator)

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

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).

3 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

FLNA was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Emory Genetics Laboratory,Expert list

3 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

FLNA was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Emory Genetics Laboratory,Expert list