Thoracic aortic aneurysm or dissectionGene: ALDH18A1
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.
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
#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
Source South West GLH was added to ALDH18A1. Mode of inheritance for gene ALDH18A1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
ALDH18A1 was added to Familial thoracic aortic aneurysms and dissectionpanel. Sources: Expert list