Ehlers Danlos syndromes

Gene: PRDM5

Green List (high evidence)

PRDM5 (PR/SET domain 5)
EnsemblGeneIds (GRCh38): ENSG00000138738
EnsemblGeneIds (GRCh37): ENSG00000138738
OMIM: 614161, Gene2Phenotype
PRDM5 is in 4 panels

6 reviews

Ivone Leong (Genomics England Curator)

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

Duncan Baker (Sheffield Genetics)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

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.

Angela Brady (Nhs)

Green List (high evidence)

Neeti Ghali (NWTRGS, Northwick Park Hospital)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

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.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert list
  • Emory Genetics Laboratory
Phenotypes
  • Brittle cornea syndrome 2, OMIM:614170
OMIM
614161
Clinvar variants
Variants in PRDM5
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

18 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: PRDM5 were changed from Brittle cornea syndrome 2, 614170; BCS; EDSVIB; Connective Tissue Disorders; Ehlers-Danlos syndrome type VIB; Brittle cornea syndrome to Brittle cornea syndrome 2, OMIM:614170

13 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to PRDM5. Rating Changed from Green List (high evidence) to Green List (high evidence)

25 Jul 2017, Gel status: 4

panel promoted to version 1

Louise Daugherty (Genomics England Curator)

25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.

26 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

7 Apr 2017, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for PRDM5 were set to 28306229; 28306225;23680354

7 Apr 2017, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for PRDM5 were set to 28306229;28306225

7 Apr 2017, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for PRDM5 were set to Brittle cornea syndrome 2, 614170; BCS;EDSVIB;Connective Tissue Disorders;Ehlers-Danlos syndrome type VIB;Brittle cornea syndrome

7 Apr 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

7 Apr 2017, Gel status: 3

Upload gene information

Louise Daugherty (Genomics England Curator)

PRDM5 was added to Ehlers-Danlos syndromespanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services

7 Apr 2017, Gel status: 1

Set Mode of Inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for PRDM5 was changed to BIALLELIC, autosomal or pseudoautosomal

24 Jan 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PRDM5 was added to Ehlers-Danlos syndromespanel. Sources: Expert list,Emory Genetics Laboratory

24 Jan 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

PRDM5 was created by ellenmcdonagh