Ehlers Danlos syndrome with a likely monogenic cause

Gene: COL9A3

I don't know

Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove the genes associated with Stickler syndrome from this panel. These genes are better covered by other panels.

Created: 11 Jun 2019, 11:07 a.m.

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: COL9A3; Suggested initial gene rating: red

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

Red List (low evidence)

d/w Dr D Johnson. Not enough phenotypic overlap with EDS for inclusion in panel.

Created: 24 Jan 2019, 12:28 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Epiphyseal dysplasia, multiple, 3, with or without myopathy 600969; Multiple epiphyseal dysplasia

Green List (high evidence)

Green List (high evidence)

Comment on mode of inheritance: Epiphyseal dysplasia, multiple, 3, with or without myopathy (AD), Stickler syndrome VI (AR)

Created: 10 May 2017, 2:58 p.m.

Review from Arianna Tucci : On panel as can present with joint laxity

Created: 10 May 2017, 12:32 p.m.

Comment on list classification: Change Red to Green from comment made by expert reviewer Allan Richards (University of Cambridge) regarding Stickler syndrome. This gene encodes the third alpha chain of the type IX collagen molecule, the other two chains being encoded by COL9A1 and COL9A2 and therefore should be rated as green even though there are not many examples in the literature. Variants in this gene are reported as part of current diagnostic practice

Created: 10 May 2017, 12:06 p.m.

Comment from Allan Richards (University of Cambridge), Oct. 16, 2015. We have unpublished confirmation of a homozygous loss of function mutation seen in COL9A3 in a patient with Stickler syndrome.
This gene encodes the third alpha chain of the type IX collagen molecule, the other two chains being encoded by COL9A1 and COL9A2 and therefore should be rated as green even though there are not many examples in the literature. Variants in this gene are reported as part of current diagnostic practice

Created: 10 May 2017, 12:04 p.m.

Comment on publications: PMID: 24273071 Faletra et al. (2014) described 3 brothers in a consanguineous Moroccan family who had some features of Stickler syndrome but who also had moderate to severe intellectual disability. The authors suggested that the mutation caused a novel form of Stickler syndrome but that it was not pathogenic for intellectual disability.

Created: 10 May 2017, 11:51 a.m.