Ehlers Danlos syndrome with a likely monogenic cause

Gene: COL1A2

Comment on phenotypes: Previous phenotypes:
Ehlers Danlos syndrome, type VIIB (AD), 130060;Ehlers-Danlos Syndrome, Arthrochalasia Type;Arthrochalasia EDS;aEDS;Ehlers Danlos syndrome, cardiac valvular form (AR), 225320;Cardiac-valvular EDS;cvEDS

Created: 18 Mar 2021, 1:43 p.m. | Last Modified: 18 Mar 2021, 1:43 p.m.

Panel Version: 2.20

Green List (high evidence)

I don't know

Comment on mode of inheritance: The mode of inheritance for Ehlers-Danlos syndrome, arthrochalasia type, 2, OMIM:617821 is monoallelic, but for Ehlers-Danlos syndrome, cardiac valvular type, OMIM:225320 it is biallelic, so it is correct that the mode of inheritance on this panel is BOTH mono- and bi-allelic.

Created: 14 Apr 2022, 10:53 a.m. | Last Modified: 14 Apr 2022, 10:53 a.m.

Panel Version: 2.65

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: COL1A2; Suggested initial gene rating: green

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

Green List (high evidence)

Green List (high evidence)

Comment on publications: Ehlers–Danlos Syndromes, Rare Types, Brady et al., 2017 (PMID:28306225): Cases with Arthrochalasia EDS Giunta et al., 2008 (PMID:18409203); Weil et al,. 1998 (PMID:2454224); Nicholls et al., 1991 (PMID:1712342); Byers et al. 1997 (PMID:9295084)
Ehlers–Danlos Syndromes, Rare Types, Brady et al., 2017 (PMID:28306225): Cases with Cardiac-valvular EDS due to variants in the gene COL1A2. To date, six patients from five independent families have been reported. Hata et al., 1988 (PMID:3383844); Kojima et al., 1988 (PMID:3049731); Nicholls et al., 2001 (PMID:11288717); Schwarze et al., 2004 (PMID:15077201); Malfait et al., 2006 (PMID:16816023).

Created: 13 Apr 2017, 12:57 p.m.

Comment on publications: The 2017 International Classification of the Ehlers–Danlos Syndromes. Malfait et al., 2017 (PMID:28306229), Ehlers–Danlos Syndromes, Rare Types. Brady et al., 2017 (PMID:28306225)

Created: 13 Apr 2017, 8:39 a.m.

In relation to the EDS pathogenetic scheme, both EDS disorders associated to COL1A2 belong to 'Disorders of collagen primary structure and collagen processing'. The scheme regroups EDS subtypes for which the proteins, coded by the causative genes, function within the same pathway, and which are likely to have shared pathogenic mechanisms, based on current knowledge.

Created: 12 Apr 2017, 2:23 p.m.

Comment on phenotypes: Amended phenotype based on updated to OMIM, Orphanet and 2017 International Classification of the Ehlers–Danlos Syndromes (PMID:28306229)

Created: 12 Apr 2017, 1:55 p.m.

Comment on mode of inheritance: COL1A2 variants that result in Cardiac-valvular EDS is a biallelic form of EDS, whereas COL1A2 variants that result in Arthrochalasia EDS is a more common monoallelic form of EDS.

Created: 12 Apr 2017, 12:38 p.m.