Journal Article


Andrea H Németh
James Hagman
Penny Clouston
Jonathan Williams
Tanya N Nelson
Anna Lehman
Linlea Armstrong
Helen Cox
Mary D King
Andrew Green
and 11 others



united kingdom strabismus metabolism humans dna canada adolescent abnormalities female infant genetics developmental disabilities age of onset ebf3 protein human male infant newborn mutation transcription factors ataxia child syndrome neurodevelopmental disorders face mutation missense intellectual disability

De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome. (2016)

Abstract Early B cell factor 3 (EBF3) is an atypical transcription factor that is thought to influence the laminar formation of the cerebral cortex. Here, we report that de novo mutations in EBF3 cause a complex neurodevelopmental syndrome. The mutations were identified in two large-scale sequencing projects: the UK Deciphering Developmental Disorders (DDD) study and the Canadian Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) study. The core phenotype includes moderate to severe intellectual disability, and many individuals exhibit cerebellar ataxia, subtle facial dysmorphism, strabismus, and vesicoureteric reflux, suggesting that EBF3 has a widespread developmental role. Pathogenic de novo variants identified in EBF3 include multiple loss-of-function and missense mutations. Structural modeling suggested that the missense mutations affect DNA binding. Functional analysis of mutant proteins with missense substitutions revealed reduced transcriptional activities and abilities to form heterodimers with wild-type EBF3. We conclude that EBF3, a transcription factor previously unknown to be associated with human disease, is important for brain and other organ development and warrants further investigation.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Andrea H Németh, James Hagman, Penny Clouston, Jonathan Williams, Tanya N Nelson, Anna Lehman, Linlea Armstrong, Helen Cox, Mary D King, Andrew Green and 11 others

Experts in our system

Mary D King
University College Dublin
Total Publications: 27
Andrew Green
University College Dublin
Total Publications: 25