Rasopathy

Gene: ERF

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome-like, MONDO:0018997, with or without craniosynostosis, ERF-related

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.
Sources: Literature

Created: 4 Jun 2024, 9:37 p.m.

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