Craniosynostosis

Gene: SIX1

Amber List (moderate evidence)

SIX1 (SIX homeobox 1)
EnsemblGeneIds (GRCh38): ENSG00000126778
EnsemblGeneIds (GRCh37): ENSG00000126778
OMIM: 601205, Gene2Phenotype
SIX1 is in 10 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

Unpublished work by AW identified 7 cases from 6 families with CSS - LOF instead of missense in BOR. Relatively common cause of mutations compared to many green genes. Known craniofacial disease gene (BOR syndrome) (AW) ; 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
sagittal synostosis, multi-suture synostosis

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 The group decided to rate Amber due to several unpublished cases.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, 4:12 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: SIX1; 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Our unpublished work has identified 5 unrelated individuals heterozygous for rare missense (n=2) or nonsense (n=3) mutations in craniosynostosis (2 de novo and 3 inherited). This represents a clear enrichment. Note that there is a distinct genotype-phenotype correlation compared with BOR syndrome, which is usually caused by missense mutations in the SIX domain. By contrast, heterozygous lof seems to be associated with a milder phenotype associated with craniosynososis in some individuals +/- mild BOR features.
Created: 18 Oct 2017, 9:02 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
sagittal synostosis, multi-suture synostosis

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • sagittal synostosis, multi-suture synostosis
OMIM
601205
Clinvar variants
Variants in SIX1
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: six1 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 SIX1.

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)

SIX1 was added to Craniosynostosis syndromes phenotypespanel. Sources: Expert Review

18 Oct 2017, Gel status: 0

Created

Andrew Wilkie (University of Oxford)

SIX1 was created by awilkie