Thoracic aortic aneurysm or dissection (GMS)
Gene: LOX
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 GreenCreated: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.
Panel Version: 0.35
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 toleratedCreated: 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
617168 Familial thoracic aortic aneursymCreated: 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
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.
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.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
aortic aneurysm
Publications
Publications for gene: LOX were set to
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)
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