Two siblings with a homozygous EEF1B2 loss-of-function variant: expanding the phenotypic spectrum of EEF1B2-related neurodevelopmental disorder

Ketenci-İşlek S., ÜREL DEMİR G., ÜTİNE G. E., ŞİMŞEK KİPER P. Ö.

Neurogenetics, vol.27, no.1, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 1
  • Publication Date: 2026
  • Doi Number: 10.1007/s10048-025-00877-w
  • Journal Name: Neurogenetics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • Keywords: EEF1B2, Global developmental delay, Intellectual disability
  • Hacettepe University Affiliated: Yes

Abstract

The eukaryotic elongation factor 1 (eEF1) complex is essential for translational elongation and comprises eEF1A and eEF1B subunits. eEF1Bα, encoded by EEF1B2, functions as the complex’s guanine nucleotide exchange factor. Recently, biallelic loss-of-function variants in EEF1B2 have been implicated in a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, behavioral abnormalities, and occasional seizures. We describe two siblings from consanguineous parents who present with profound developmental delay, severe speech impairment, and additional neurodevelopmental features. Whole-exome sequencing identified a homozygous nonsense variant in EEF1B2, classified as likely pathogenic. These cases expand the phenotypic spectrum of EEF1B2-related disease.