Thoracic aortic aneurysm or dissection (GMS)
Gene: ASPH
The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 3:25 p.m. | Last Modified: 30 Jan 2023, 3:25 p.m.
Panel Version: 2.3
Comment on list classification: Promoting this gene from grey to amber but with a recommendation for a green rating following GMS review. There are sufficient cases with a cardiac phenotype relevant to this panel.Created: 28 Sep 2022, 5:11 p.m. | Last Modified: 28 Sep 2022, 5:11 p.m.
Panel Version: 1.26
Associated with Traboulsi syndrome #601552 (AR) in OMIM.
As described by Simon Thomas Jones et al 2022 (PMID: 35918038) reports 7 individuals from 6 families (patients 2 and 3 related) with homozygous or compound het variants in ASPH. All presented initially with ocular phenotypes and had characteristic facial features seen in Traboulsi syndrome, but 5 patients from 4 families were additionally found to have aortic dilatation as part of their clinical characteristics. The two siblings had small deletion in ASPH c.1497_1500delGGCA p.(Lys499Asnfs*12), 3 probands from apparently unrelated families of British Pakistani or Pakistani origin had a duplication c.2181_2183dupATG, p.(Trp728*), and one individual had a nonsense variant plus a larger deletion c.2062C>T, p.(Arg688*); 8q12.3 deletion (GRCh38 61294555–61691830).
One other individual had a homozygous synonymous variant in ASPH that is thought to affect the strength of a splice donor site. This patient did not have a cardiac phenotype.Created: 28 Sep 2022, 5:08 p.m. | Last Modified: 28 Sep 2022, 5:08 p.m.
Panel Version: 1.23
Biallelic variants in ASPH are associated with Traboulsi syndrome Jones et al (PMID: 35918038) report seven further individuals from six apparently unrelated families identified through genetics clinics with confirmed molecular diagnoses and features consistent with Traboulsi syndrome. These patients exhibited additional cardiac, musculoskeletal and haematological features thus expanding the phenotypic spectrum of Traboulsi syndrome and demonstrating considerable overlap with Marfan syndrome. Specifically, five individuals had aortic root dilatation, with childhood onset in some, and one undergoing aortic root repair aged 47 years for severe aortic regurgitation and aortic root dilatation. Therefore ASPH should be considered for inclusion in the R125 TAAD/Marfan panel.
Sources: LiteratureCreated: 21 Sep 2022, 8:11 a.m. | Last Modified: 21 Sep 2022, 8:12 a.m.
Panel Version: 1.23
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
ocular features; anterior segment abnormalities; distinctive facial appearance; aortic root dilatation
Publications
Tag Q3_22_rating was removed from gene: ASPH. Tag Q3_22_MOI was removed from gene: ASPH. Tag Q3_22_NHS_review was removed from gene: ASPH.
Source Expert Review Green was added to ASPH. Source NHS GMS was added to ASPH. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: asph has been classified as Amber List (Moderate Evidence).
Tag Q3_22_rating tag was added to gene: ASPH. Tag Q3_22_MOI tag was added to gene: ASPH. Tag Q3_22_NHS_review tag was added to gene: ASPH.
Phenotypes for gene: ASPH were changed from ocular features; anterior segment abnormalities; distinctive facial appearance; aortic root dilatation to Traboulsi syndrome, OMIM:601552; facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome, MONDO:0011106
Publications for gene: ASPH were set to PMID: 35918038
gene: ASPH was added gene: ASPH was added to Thoracic aortic aneurysm and dissection. Sources: Literature Mode of inheritance for gene: ASPH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASPH were set to PMID: 35918038 Phenotypes for gene: ASPH were set to ocular features; anterior segment abnormalities; distinctive facial appearance; aortic root dilatation Penetrance for gene: ASPH were set to unknown