Ehlers Danlos syndrome with a likely monogenic cause

Gene: ABL1

Comment 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

Green List (high evidence)

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: Literature

Created: 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

• 28288113

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments