Craniosynostosis

Gene: ALX4

Green List (high evidence)

ALX4 (ALX homeobox 4)
EnsemblGeneIds (GRCh38): ENSG00000052850
EnsemblGeneIds (GRCh37): ENSG00000052850
OMIM: 605420, Gene2Phenotype
ALX4 is in 6 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Coronal CSS noted in 2 consanguineous families with AR FND2 (same mut) but NOT in a third family. CSS not a feature of AD PF. 2 inherited non-penetrant missense variants also seen in 2 unrelated cases with non-syndromic CSS. Suggested green status takes into account knowledge of several unpublished cases with CSS (AW) ; Review on behalf of Tracy Lester/Andrew Wilkie
Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Parietal foramina; Parietal foramina 2, (AD), 609597; Frontonasal dysplasia 2, (AR), 613451

Publications

Variants in this GENE are reported as part of current diagnostic practice

Eleanor Williams (Genomics England Curator)

I don't know

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: ALX4; Suggested initial gene rating: green
Created: 5 Mar 2019, 11:21 a.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: changed from Red to Green due to new evidence in the literature for craniosynostosis
Created: 13 Aug 2018, 4:19 p.m.
Comment on publications: Added publications El-Ruby et al., 2018 (PMID: 29681084) and Lee et al., (2017) PMID:29215649 to support upgrading of the gene to Green
Created: 13 Aug 2018, 4:14 p.m.
Comment on phenotypes: added phenotype suggested by reviewer and OMIM relevant to the panel
Created: 13 Aug 2018, 4:12 p.m.
PMID: 29215649 and PMID:29681084
novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type-2.
Created: 13 Aug 2018, 4:05 p.m.

Andrew Wilkie (University of Oxford)

Red List (low evidence)

The Yagnik paper describes association with craniosynostosis and some functional evidence. Most heterozygous loss-of-function mutations in ALX4 cause parietal foramina, but association of craniosynostosis with particular mutations is feasible and supported by unpublished data from Wilkie lab
Created: 14 Sep 2015, 1:57 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
parietal foramina

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert list
Phenotypes
  • Parietal foramina
  • Parietal foramina 2, (AD), 609597
  • Frontonasal dysplasia 2, (AR), 613451
OMIM
605420
Clinvar variants
Variants in ALX4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

5 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to ALX4. Rating Changed from Green List (high evidence) to Green List (high evidence)

14 Aug 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ALX4 were set to Parietal foramina; Parietal foramina 2, (AD), 609597; Frontonasal dysplasia 2, (AR), 613451

13 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: alx4 has been classified as Green List (High Evidence).

13 Aug 2018, Gel status: 1

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: ALX4 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

13 Aug 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ALX4 were set to 22829454; 29681084; 29215649

13 Aug 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ALX4 were set to 22829454; 29681084, 29215649

13 Aug 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ALX4 were set to Parietal foramina; Parietal foramina 2, (AD), 609597; Frontonasal dysplasia 2, (AR), 613451

13 Aug 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ALX4 were set to Parietal foramina; Parietal foramina 2, (AD) 609597; Frontonasal dysplasia 2, (AR) 613451

1 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

27 Jul 2015, Gel status: 0

Added New Source

Eik Haraldsdottir (Genomics England)

ALX4 was added to Craniosynostosis syndromespanel. Sources: Expert list