Ehlers Danlos syndrome with a likely monogenic cause
Gene: ABL1Comment on list classification: Downgrading from Green to Amber on advice of Neeti Ghali and Fleur Dijk who are part of the GMS Musculoskeletal specialist test group. They advise that it does not need to be green on the EDS panel.Created: 31 Jul 2019, 10:57 a.m. | Last Modified: 31 Jul 2019, 11:24 a.m.
Panel Version: 1.61
Comment on mode of pathogenicity: Seleced 'LOF do not cause this phenotype' on advice from Helen Brittain, Clinical Fellow, in view of the postulated gain of function mechanism (two recurent missense variants).Created: 6 Dec 2018, 9:19 p.m.
Comment on list classification: Rated as Green as advised by Helen Brittain based on relevant EDS-like phenotype, and sufficient cases see in PMID:28288113.Created: 6 Dec 2018, 9:18 p.m.
Added ABL1 to EDS panel as requested by Helen Brittain, clinical fellow. Wang et al, 2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. 2 variants reported in 4 families, including c.734A>G (p.Tyr245Cys) found to occur in 3 famililes. Included on this EDS panel on advice from Helen Brittain: the kyphosis / scoliosis / velvety skin could overlap with the EDS syndromes panel as a mimic of kyphoscoliotic EDS.
Sources: LiteratureCreated: 6 Dec 2018, 9:18 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Congenital heart defects and skeletal malformations syndrome, 617602
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phenotypes for gene: ABL1 were changed from Congenital heart defects and skeletal malformations syndrome, 617602 to Congenital heart defects and skeletal malformations syndrome, OMIM:617602
Gene: abl1 has been classified as Amber List (Moderate Evidence).
Mode of pathogenicity for gene: ABL1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: abl1 has been classified as Green List (High Evidence).
gene: ABL1 was added gene: ABL1 was added to Ehlers Danlos syndromes. Sources: Literature missense tags were added to gene: ABL1. Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ABL1 were set to 28288113 Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome, 617602 Mode of pathogenicity for gene: ABL1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ABL1 was set to GREEN