Ehlers Danlos syndrome with a likely monogenic cause

Gene: AEBP1

Comment on phenotypes: Previous phenotypes:
Ehlers-Danlos syndrome type;EDS type;Part of the EDS spectrum

Created: 18 Mar 2021, 1:16 p.m. | Last Modified: 18 Mar 2021, 1:16 p.m.

Panel Version: 2.6

Green List (high evidence)

I don't know

This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: AEBP1; Suggested initial gene rating: green

Created: 3 Apr 2019, 3:41 p.m.

Green List (high evidence)

Comment on list classification: Changed from Amber to Green due to external clinical review

Created: 18 Apr 2018, 9:29 a.m.

Re: PMID:29606302 (2018). Feedback via email from combined external expert review Neeti Ghali, Angela Brady and Fleur Dijk (LONDON NORTH WEST UNIVERSITY HEALTHCARE NHS TRUST) agree this gene should be rated Green on this panel. They also noted that the specific EDS classification type is not clear, as the authors of the article (extremely well-known in the EDS field) conclude at present for it to be a disorder part of the EDS spectrum. This is because the clinical phenotype in affected individuals overlaps with several subtypes, mostly classical, vascular and arthrochalasia subtype but also kyphoscoliotic and this is because there is the presence of both major and minor criteria for these subtypes: severe joint and skin laxity, osteoporosis, osteoarthritis, soft redundant skin, delayed wound healing with abnormal atrophic scarring and dislocations.

Created: 18 Apr 2018, 9:27 a.m.

Re: PMID:29606302 (2018). Feedback via email from external expert Antony Vandersteen (IWK Health Center and Dalhousie University, Nova Scotia, Canada ) agrees this gene should be rated Green on this panel, since the clinical, molecular, histological and biochemical findings support EDS phenotype

Created: 18 Apr 2018, 9:26 a.m.

Comment on list classification: Changed from Green to Amber until we have external clinical review of this gene being associated to EDS. The evidence in PMID: 29606302 is strong but as new EDS gene it would be good to get expert opinion.

Created: 3 Apr 2018, 4:10 p.m.

Comment on publications: added PMID 29606302

Created: 3 Apr 2018, 4:07 p.m.

Green List (high evidence)

Comment on list classification: Awaiting confirmation from EDS expert reviewers

Created: 3 Apr 2018, 4:40 p.m.

Comment on publications: PMID not available to date

Created: 3 Apr 2018, 3:41 p.m.

Not associated with phenotype in OMIM nor Gen2Phen. Four variants reported in three unrelated cases (two as compound heterozygotes and two as homozygotes). All four variants are likely pathogenic (3 truncating and 1 splicing) and the authors provide functional studies stating that "ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain", they also state that "bi-allelic pathogenic variants in AEBP1 cause the particular autosomal-recessive EDS subtype reported in this article. (Sub-type to be confirmed but the EDS community)

Created: 3 Apr 2018, 3:40 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
autosomal-recessive EDS subtype

Publications

• https://doi-org.ezproxy.library.qmul.ac.uk/10.1016/j.ajhg.2018.02.018