Intellectual disability syndromic and non-syndromic
Gene: ERF

ERF (ETS2 repressor factor)
EnsemblGeneIds (GRCh38): ENSG00000105722
EnsemblGeneIds (GRCh37): ENSG00000105722
OMIM: 611888, Gene2Phenotype
ERF is in 7 panels

2 reviews

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

ERF gene encodes a transcriptional regulator negatively controlling RAS-MAPK signalling. It has been associated with syndromic craniosynostosis involving various cranial sutures and Chitayat syndrome (respiratory distress, skeletal anomalies, and facial dysmorphism).

This paper describes 26 individuals from 15 unrelated families with Noonan-syndrome (NS) like phenotype and heterozygous nonsense and frameshift variants in ERF (most cases were familial). The clinical features included: variable global developmental and/or language delay, absolute/relative macrocephaly, short stature (<3rd centile), and dysmorphism (high forehead, hypertelorism, ptosis, wide nasal bridge, and low-set/posteriorly angulated ears). There were no individuals with typical NS cardiac involvement. Craniosynostosis was only seen in 3/26 unrelated individuals.

These findings provide evidence that heterozygous loss-of-function variants in ERF cause a "RASopathy" resembling NS with or without craniosynostosis.
Created: 4 Jun 2024, 9:39 p.m. | Last Modified: 4 Jun 2024, 9:39 p.m.

Panel Version: 0.6020

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome-like with or without craniosynostosis

Publications

PMID: 38824261

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

Created: 4 Jun 2024, 9:39 p.m.
Last Modified: 4 Jun 2024, 9:39 p.m.
Panel version: 0.6020

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

ID is not really part of the phenotype of either condition; mild learning difficulties described in some individuals affected by craniosynostosis 4.
Created: 1 Dec 2019, 7:23 p.m. | Last Modified: 1 Dec 2019, 7:23 p.m.

Panel Version: 0.173

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Chitayat syndrome, MIM#617180; Craniosynostosis 4, MIM#600775

Created: 1 Dec 2019, 7:23 p.m.
Last Modified: 1 Dec 2019, 7:23 p.m.
Panel version: 0.173

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Genetic Health Queensland

Phenotypes

Chitayat syndrome, MIM#617180
Craniosynostosis 4, MIM#600775

OMIM

611888

Clinvar variants

Variants in ERF

Penetrance

None

Panels with this gene

History Filter Activity

4 Jun 2024, Gel status: 3

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

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

1 Dec 2019, Gel status: 1