Thoracic aortic aneurysm or dissection

Gene: LOX

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

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.

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

• 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