Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features

Area of Science:

• Genetics
• Neurodevelopmental Biology
• Human Molecular Genetics

Background:

• Intellectual disability and developmental delay are significant neurodevelopmental concerns.
• Human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2) has been previously implicated in a small number of patients with these conditions.
• HIVEP2 is a transcription factor crucial for regulating neurodevelopmental pathways.

Purpose of the Study:

• To investigate the role of HIVEP2 in a cohort of patients presenting with developmental delay, intellectual disability, and dysmorphic features.
• To identify potential de novo gene-damaging variants in HIVEP2 associated with these neurodevelopmental phenotypes.

Main Methods:

• Whole-exome sequencing (WES) was employed to analyze the genetic profiles of affected individuals.
• Variant calling and pathogenicity assessment were performed to identify likely gene-damaging mutations in HIVEP2.
• Clinical data, including developmental assessments and dysmorphological evaluation, were correlated with genetic findings.

Main Results:

• Six new patients with developmental delay, intellectual disability, and dysmorphic features were identified.
• De novo likely gene-damaging variants in HIVEP2 were detected in all six patients.
• These findings expand the spectrum of HIVEP2-associated neurodevelopmental disorders.

Conclusions:

• Pathogenic variants in HIVEP2 are a confirmed cause of intellectual disability and developmental delay.
• HIVEP2 plays a critical role in human neurodevelopment.
• Genetic analysis, particularly WES, is effective in identifying causative genes for neurodevelopmental disorders.