Craniosynostosis

Gene: PRRX1

Amber List (moderate evidence)

PRRX1 (paired related homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000116132
EnsemblGeneIds (GRCh37): ENSG00000116132
OMIM: 167420, Gene2Phenotype
PRRX1 is in 3 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

Unpublished work by AW found relatively common cause of mutations compared to many green genes, currently aware of 8 unrelated unpublished cases with CSS, 1 de novo and 7 inherited from unaffected parent (AW). Similar variants seen in agnathia-otocephaly phenotype (TL). ; Review on behalf of Tracy Lester and Andrew Wilkie
Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
craniosynostosis, various combinations of sutures

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Upgrading from red to amber. Amber rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13. The group decided to rate Amber due to several unpublished cases.
Created: 21 May 2019, 4:10 p.m.
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: PRRX1; Suggested initial gene rating: amber
Created: 5 Mar 2019, 11:21 a.m.

Andrew Wilkie (University of Oxford)

Red List (low evidence)

Our unpublished work has identified PRRX1 mutations in 6 unrelated individuals/families. Mutations are either heterozygous lof or missense changes in highly conserved homeodomain. Only one of the six mutations is de novo, remainder inherited from often clinically minimally affected parent. Note very marked contrast between these findings and previous reports of a similar spectrum of mutations causing agnathia-otocephaly; the reasons underlying this discrepancy remain unclear.
Created: 18 Oct 2017, 9:07 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
craniosynostosis, various combinations of sutures

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • craniosynostosis, various combinations of sutures
OMIM
167420
Clinvar variants
Variants in PRRX1
Penetrance
Complete
Panels with this gene

History Filter Activity

21 May 2019, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: prrx1 has been classified as Amber List (Moderate Evidence).

5 Mar 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to PRRX1.

20 Oct 2017, Gel status: 0

Approved Gene

Ellen McDonagh (Genomics England Curator)

This proposed gene was validated and added to this panel

18 Oct 2017, Gel status: 0

Added New Source

Andrew Wilkie (University of Oxford)

PRRX1 was added to Craniosynostosis syndromes phenotypespanel. Sources: Expert Review

18 Oct 2017, Gel status: 0

Created

Andrew Wilkie (University of Oxford)

PRRX1 was created by awilkie