Multiple Epiphyseal Dysplasia

Gene: COL9A1

Green List (high evidence)

Green List (high evidence)

Comment on list classification: MED-related mutation only reported in one study, therefore this gene should be on the red list.

Created: 8 Feb 2016, 1:31 p.m.

PMID: 11565064: report a variant in COL9A1 (T insertion at the donor splice site of IVS8+3) found in a proband with MED and affected mother, but not in unaffected sister. Sequencing data, restriction digest, pedigree, and analysis in mother or sister are not shown in the publication.

There seems to be several studies since that have not found variants within the COL9A1 gene associated with MED: PMID: 21922596 - n=77 patients with suspected autosomal-dominant MED; PMID: 15523498 - no disease-causing mutations were found in exons 8-10 of COL9A1 in 30 unrelated patients; PMID: PMID: 14684695 no disease-causing mutations were found in exons 8-10 of COL9A1 in two families; PMID: 10678658 - none found in COL9A1 in a multi-generation family study; PMID: 20358595 - exon 8 of COL9A1 found no mutations in two families; PMID: 16691584 - no mutations found in COL9A1 in 33 patients.

Created: 8 Feb 2016, 1:29 p.m.

Comment on mode of pathogenicity: See comments by reviewer.

Created: 5 Feb 2016, 3:21 p.m.

Comment on mode of inheritance: Confirmed on G2P and OMIM, and not on imprinted gene list.

Created: 5 Feb 2016, 3:18 p.m.

Comment on list classification: Confirmed DD gene.

Created: 5 Feb 2016, 3:17 p.m.

Green List (high evidence)

Despite a COL9A1 mutation only being identified in 1 MED family, there is good biological evidence that this mutation is located in an important functional domain of type IX collagen i.e. the COL3 domain. Moreover, the mutations in COL9A2 and COL9A3 affect the equivalent amino acid residues in this COL3 domain. This precise clustering of COL9A1, COL9A2 and COL9A3 mutations to the same residues of COL3 domain of type IX collagen is an important functional finding that should not be ignored.

Created: 12 Apr 2016, 2:42 p.m.

A mutation in COL9A1 has only been reported in a single family with MED. Dominant-negative mutation due to presumed exon skipping and in-frame deletion of part of the COL3 domain of type IX collagen.

Created: 9 Oct 2015, 10:03 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Mode of pathogenicity
Other