Thoracic aortic aneurysm and dissection

Gene: LOX

Green List (high evidence)

LOX (lysyl oxidase)
EnsemblGeneIds (GRCh38): ENSG00000113083
EnsemblGeneIds (GRCh37): ENSG00000113083
OMIM: 153455, Gene2Phenotype
LOX is in 5 panels

7 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

James Eden (Manchester)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Aortic aneurysm, familial thoracic 10 617168

Publications

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

Green List (high evidence)

On CGGL Royal Brompton FTAAD panel. Likely pathogenic variants detected where dilated aortic root and h/o pneumothorax were presenting features.
Missense and truncating variants described in the literature segregating with disease in several families, and reported by other diagnostic laboratories (eg: OMIM ref 153455; Lee et al (2016) Proc Natl Acad Sci 113(31):8759-8764; Guo et al (2016) Circ Res 118(6):928-34; ClinVar IDs 489315, 424133). ExAC LOF pLi score for LOX is 0.98, suggesting that LOF is not tolerated
Created: 18 Sep 2019, 7:47 p.m. | Last Modified: 18 Sep 2019, 7:47 p.m.
Panel Version: 0.30

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
OMIM: 617168 Aortic aneurysm, familial thoracic 10

Publications

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

Rebecca Whittington (South West GLH)

Green List (high evidence)

617168 Familial thoracic aortic aneursym
Created: 25 Mar 2019, 4:30 p.m.
Guo et al 2016 Circ Res 118:928 PMID:26838787 LOX c.839G>T (p.Ser280Arg) segregates with FTAAD in a large family and other variants also show segregation in other families c.125G>A (p.Trp42*), c.604G>T (p.Gly202*), c.743C>T (p.Thr248Ile), c.800A>C (p.Gln267Pro), and c.1044T>A (p.Ser348Arg). Some (but not all) patients had additional Marfaniod features.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

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 LOX as ready: July 4th 2017.
Created: 4 Jul 2017, 2:59 p.m.
Comment on list classification: Updated rating from grey to green. Green review from gene submitter (Bill Newman) and >3 unrelated cases supporting causation. Plus on the ClinGen 'Familial thoracic aortic aneurysm and aortic dissection' (TAAD) panel with Strong evidence (https://search.clinicalgenome.org/kb/gene-validity).
Created: 4 Jul 2017, 2:59 p.m.
Comment on mode of inheritance: Monoallelic mode of inheritance confirmed by OMIM and literature.
Created: 26 Jun 2017, 12:35 p.m.
>3 unrelated cases supporting causation from two 2016 papers: PMID:26838787: WES in one family with thoracic aortic aneurysm and aortic dissection (TAAD) identified a rare coding variant in LOX. Exome and/or Sanger sequencing of LOX from 410 additional probands found 8 rare coding variants. PMID:27432961: WES in two first cousins with TAAD identified a rare missense mutation (M298R) in LOX that co-segregated with disease.
Created: 26 Jun 2017, 12:35 p.m.

Bill Newman (Manchester Centre for Genomic Medicine)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
aortic aneurysm

Publications

  • Circ Res. 2016 Mar 18
  • 118(6):928-34. doi: 10.1161/CIRCRESAHA.115.307130. PMID: 26838787
  • Proc Natl Acad Sci U S A. 2016 Aug 2
  • 113(31):8759-64. doi: 10.1073/pnas.1601442113. PMID: 27432961

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • NHS GMS
  • Expert Review Green
  • South West GLH
  • London South GLH
  • South West GLH
  • London South GLH
Phenotypes
  • Aortic aneurysm, familial thoracic 10, 617168
  • aortic aneurysm
OMIM
153455
Clinvar variants
Variants in LOX
Penetrance
None
Publications
Panels with this gene

History Filter Activity

18 Nov 2019, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: LOX were set to

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

18 Apr 2019, Gel status: 2

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

Ellen McDonagh (Genomics England Curator)

gene: LOX was added gene: LOX was added to GMS FTAAD placeholder panel. Sources: Expert Review Amber,London South GLH,South West GLH Mode of inheritance for gene: LOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LOX were set to Aortic aneurysm, familial thoracic 10, 617168; aortic aneurysm