Ehlers Danlos syndrome with a likely monogenic cause
Gene: COL9A3
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: redCreated: 3 Apr 2019, 3:41 p.m.
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
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 laxityCreated: 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 practiceCreated: 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 We have unpublished confirmation of a homozygous loss of function mutation seen in COL9A3 in a patient with Stickler syndrome.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 practiceCreated: 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.
Tag curated_removed tag was added to gene: COL9A3.
Gene: col9a3 has been removed from the panel.
Phenotypes for gene: COL9A3 were changed from Stickler syndrome VI; Connective Tissue Disorders; Epiphyseal dysplasia, multiple, 3, with or without myopathy, 600969 to Stickler syndrome VI; Connective Tissue Disorders; Epiphyseal dysplasia, multiple, 3, with or without myopathy, 600969; Multiple epiphyseal dysplasia
Source NHS GMS was added to COL9A3. Rating Changed from Green List (high evidence) to Green List (high evidence)
25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.
Mode of inheritance for COL9A3 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for COL9A3 were set to 24273071; 20301479;10090888;10655510;15551337
This gene has been classified as Green List (High Evidence).
Publications for COL9A3 were set to 24273071; 20301479
Phenotypes for COL9A3 were set to Stickler syndrome VI; Connective Tissue Disorders;Epiphyseal dysplasia, multiple, 3, with or without myopathy, 600969
Publications for COL9A3 were set to 21671392; 24273071; 20301479
Publications for COL9A3 were set to 21671392;24273071
Phenotypes for COL9A3 were set to ?Stickler syndrome type; Connective Tissue Disorders
Mode of inheritance for COL9A3 was changed to BIALLELIC, autosomal or pseudoautosomal
COL9A3 was added to Ehlers-Danlos syndromespanel. Sources: Expert list
COL9A3 was created by ellenmcdonagh