EEF1D-Associated Neurodevelopmental Disorders: Evidence From Iranian Siblings With a Biallelic Splice Junction Loss Variant.

backgroundGlobal developmental delay (GDD) and intellectual disability (ID) are neurodevelopmental conditions with significant phenotypic and genetic heterogeneity. EEF1D (OMIM* 130592) has recently been identified as a gene of interest in neurodevelopmental disorders. Neurodevelopmental disorder with thin corpus callosum, hypotonia, and absent language (NEDTCHAL) (OMIM #621150) is caused by homozygous or compound heterozygous disease-causing variants in the EEF1D.

methodsWe performed whole exome sequencing (WES) on an Iranian sibling presenting with global developmental delay, intellectual disability, microcephaly, and failure to thrive. Bioinformatic analysis and Sanger sequencing were used to validate and characterize the identified variant.

resultsA novel homozygous splicing variant in EEF1D (c.1489-26_1493del) was identified in both affected individuals. The variant is predicted to disrupt splicing and cause a frameshift deletion. Previous studies have implicated biallelic EEF1D variants in neurodevelopmental disorders, and this report is the first from the Iranian population and the seventh family to be reported worldwide with this rare condition.

conclusionThis report provides further evidence for the association between EEF1D variants and neurodevelopmental disorders, expanding the phenotypic spectrum of EEF1D-related conditions. It reinforces the importance of recognizing EEF1D as a key gene involved in developmental delay and intellectual disability.