Novel biallelic loss of EEF1B2 function links to autosomal recessive intellectual disability

Abstract

Biallelic variants in EEF1B2 have recently been shown to cause a novel form of non-syndromic intellectual disability (ID) in two unrelated families. More patients are needed to delineate the genotypic and phenotypic spectrum of this gene. In this study, two patients in a family harboring pathogenic compound heterozygous variants in EEF1B2 were identified. They were characterized by non-syndromic ID and fever-sensitive seizures in childhood. Quantitative real-time polymerase chain reaction (QPCR) analysis showed significantly reduced levels of mRNA expression in two patients compared with unaffected controls. The level of EEF1B2 protein was hardly detected in both patients and their unaffected parents. The eef1b2 F0 knockout (crispant) zebrafish presented with abnormal development and light-induced hyperactivity. We identified novel pathogenic EEF1B2 variants within two siblings in a new family. The findings of the expression experiment and first crispant eef1b2 zebrafish model provided further clues to the role of EEF1B2 variants in the pathogenesis of autosomal-recessive ID.

Keywords: EEF1B2; biallelic pathogenic variants; intellectual disability; neurodevelopmental disorders; seizures.