New evidence that biallelic loss of function in EEF1B2 gene leads to intellectual disability.

The guanine exchange factor subunit eEF1Bα encoded by the EEF1B2 gene belongs to the eukaryotic elongation translational machinery. Pathogen variants in genes of the translational machinery have been associated with several neurodevelopmental disorders. However, only one family of three siblings with intellectual disability (ID) has been reported so far with a homozygous variant in EEF1B2.

NR4A2 haploinsufficiency is associated with intellectual disability and autism spectrum disorder.

NR4A2, a member of the nuclear receptor superfamily, is involved in modulation of target gene transcription, regulating several developmental processes such as regulation of cellular homeostasis, neuronal development, inflammation and carcinogenesis. 2q24.1 deletions are extremely rare, and only 1 patient with a de novo deletion encompassing only NR4A2 gene was reported so far.

EFNB2 haploinsufficiency causes a syndromic neurodevelopmental disorder.

Ephrin B2, one of the ligand of the EphB receptors, is involved in a complex signaling pathway regulating the development of the nervous system, neuronal migration, erythropoiesis and vasculogenesis. We report a patient with a de novo variant in EFNB2 and a family in which segregates a 610-kb deletion at chromosome 13q33 encompassing only ARGLU1 and EFNB2 genes. The de novo variant was observed in a patient with anal stenosis, hypoplastic left ventricle and mild developmental delay.