Ehlers Danlos syndrome with a likely monogenic cause

Gene: PRDM5

Comment on phenotypes: Previous phenotypes:
Brittle cornea syndrome 2, 614170;BCS;EDSVIB;Connective Tissue Disorders;Ehlers-Danlos syndrome type VIB;Brittle cornea syndrome

Created: 18 Mar 2021, 1:56 p.m. | Last Modified: 18 Mar 2021, 1:56 p.m.

Panel Version: 2.38

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: PRDM5; Suggested initial gene rating: green

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

Green List (high evidence)

Green List (high evidence)

Green List (high evidence)

Comment on list classification: Changed status from Amber to Green from Review from Dr Anthony Vandersteen, IWK Health centre in Halifax, Nova Scotia, Canada

Created: 26 Apr 2017, 9:41 a.m.

Review from Dr Anthony Vandersteen, IWK Health centre in Halifax, Nova Scotia, Canada 'The brittle cornea syndrome is discussed in the new nosology and greatly overlaps with kyphoscoliotic EDS, so I would put PRDM5 and ZNF469 as green'

Created: 26 Apr 2017, 9:41 a.m.

Comment on list classification: Awaiting expert review on whether this can be made Green

Created: 7 Apr 2017, 2:30 p.m.

To provide a comprehensive overview of the clinical phenotype of Brittle Cornea Syndrome, a review of reported cases was undertaken that analysed 51 patients (ZNF469: n=32; PRDM5: n=32), although the the hallmarks of the condition was thin, fragile cornea, with an increased risk for spontaneous corneal rupture, other observed phenotypes such as Craniofacial involvement, Musculoskeletal system, Skin and integument, hearing and cardiovascular were observed less consistently. So currently there is no evidence of a clear genotype–phenotype correlation as all types of mutations scattered across both genes appear to cause indistinguishable clinical phenotypes (PMID:28306225)

Created: 7 Apr 2017, 2:29 p.m.

Comment on publications: added publication to support there may be another gene responsible for the BCS phenotype

Created: 7 Apr 2017, 2:28 p.m.

Brittle Cornea Syndrome (BCS) is caused by biallelic mutations in either the genes PRDM5 encoding a DNA- binding transcription factor of the PR/ SET protein family that lacks the intrinsic histon methyltransferase activity or ZNF469, encoding a zinc finger protein of unknown function . At least one family with a clinical BCS phenotype did not harbor mutations in these genes, suggesting that at least one other gene might be associated with BCS (Rohrbach et al., 2013 PMID:23680354).

Created: 7 Apr 2017, 2:26 p.m.

In relation to the EDS pathogenetic scheme, PRDM5 belongs to 'Disorders of intracellular processes'. 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. However, for EDS subtypes implemented in the Disorders of intracellular processes catagory (subtypes included: Spondylocheirodysplastic EDS and Brittle Cornea Syndrome), the underlying pathophysiological mechanism currently is not readily understood, and classification within this subgroup is provisionary, until further functional information becomes available (PMID:28306229).

Created: 7 Apr 2017, 2:25 p.m.

Comment on publications: Comment on publications: Added from 2017 International Classification of the Ehlers–Danlos Syndromes (PMID:28306229) and The Ehlers–Danlos Syndromes, rare types (PMID:28306225)

Created: 7 Apr 2017, 2:25 p.m.

Comment on phenotypes: added synonyms / phenotypes from the literature

Created: 7 Apr 2017, 2:24 p.m.

This is a rare recessive form of EDS

Created: 30 Mar 2017, 11:22 a.m.