Thoracic aortic aneurysm or dissection (GMS)

Gene: ALDH18A1

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.

Created: 18 Nov 2019, 4:33 p.m. | Last Modified: 18 Nov 2019, 4:33 p.m.

Panel Version: 0.35

Red List (low evidence)

Not significantly associated with aortopathy.

Created: 2 Oct 2019, 3:31 p.m. | Last Modified: 2 Oct 2019, 3:31 p.m.

Panel Version: 0.32

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cutis laxa, autosomal dominant 3 616603; Cutis laxa, autosomal recessive, type IIIA 219150; Spastic paraplegia 9A, autosomal dominant 601162; Spastic paraplegia 9B, autosomal recessive 616586

Red List (low evidence)

AD (606603)/AR (219150) cutis laxa; rarely associated with aortic insufficiency or thin aortic valve. Dislocations; joint laxity; spinal curvature; thin translucent lax skin are all features which overlap some of the MFS/EDS spectrum of syndromes.

Created: 25 Mar 2019, 4:30 p.m.

Publications support role for this gene in a cutis laxa phenotype, e.g. Fischer-Zernsak et al (Am J Hum Genet 2015 97:483 PMID:26320891) which shows 3 different de novo variants affecting the same nucleotide in 8 families with a progeroid presentation of AD cutis laxa. No aortic involvement so insufficient to justify inclusion on panel unless overlapping features with relevant diseases is considered.

Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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, 10:52 a.m.

Red List (low evidence)

No association with aneurysm formation. From GeneReviews: ALDH18A1-related cutis laxa (ARCL3A) (OMIM 219150). A syndrome of IUGR, cataracts, postnatal growth failure and developmental delay with cutis laxa has been described in two pedigrees. Joint hyperlaxity is apparently a common feature. This syndrome falls within de Barsy syndrome spectrum. It is associated with pathogenic variants in ALDH18A1, previously known as P5CS, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS) [Baumgartner et al 2000, Baumgartner et al 2005, Bicknell et al 2008].

Created: 11 Feb 2016, 1:10 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
#616603- cutis laxa, autosomal dominant 3; #219150- Cutis laxa, autosomal recessive, type IIIA; #601162-Spastic paraplegia 9A, autosomal dominant; #616586- Spastic paraplegia 9B, autosomal recessive

Publications

• PMID: 18478038