Thoracic aortic aneurysm or dissection

Gene: LOX

Green List (high evidence)

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

4 reviews

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
  • South West GLH
  • London South GLH
  • Expert Review Green
Phenotypes
  • aortic aneurysm
  • Aortic aneurysm, familial thoracic 10, 617168
OMIM
153455
Clinvar variants
Variants in LOX
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 LOX.

20 Feb 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

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

4 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

4 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

26 Jun 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

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

26 Jun 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for LOX were set to 26838787; 27432961

26 Jun 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for LOX were set to aortic aneurysm; Aortic aneurysm, familial thoracic 10, 617168

10 Mar 2017, Gel status: 0

Added New Source

Bill Newman (Manchester Centre for Genomic Medicine)

LOX was added to Familial Thoracic Aortic Aneurysm Diseasepanel. Sources: Literature

10 Mar 2017, Gel status: 0

Created

Bill Newman (Manchester Centre for Genomic Medicine)

LOX was created by Reviewer_05