A nonsense variant in the C-terminal transactivation domain of the EBF3 gene in an individual with intellectual disability and behavioural disorder: case report and literature review.

Abstract

Heterozygous variants in the Early B cell factor 3 (EBF3) have been reported in individuals presenting with hypotonia, ataxia and delayed development syndrome (HADDS) (MIM#617330). However, individuals with pathogenic variants in EBF3 show phenotypic heterogeneity and very few variants in the C-terminal domain have been described. We report on a heterozygous de-novo variant in the EBF3 gene in an individual with neurodevelopmental delay and behavioural problems. The proband presented with speech delay, learning disability and behavioural problems that suggest an oppositional defiant disorder. He also has hyperactivity, irritability, hetero-aggressiveness, visual hallucinations, insomnia and decreased pain sensitivity. Whole exome sequencing revealed a de-novo heterozygous nonsense variant - c.1408C>T (p.Arg470*) - in the EBF3 gene, classified as pathogenic. The patient herein described, with a truncating variant in the C-terminal domain of EBF3, supports the clinical variability of this condition and contributes to genotype-phenotype correlation of this rare disorder.