A novel homozygous truncating variant in PPFIBP1 further delineates PPFIBP1-associated neurodevelopmental disorder.

Neurodevelopmental disorders (NDDs) are classified as a group of disorders affecting function and development of the brain and having wide clinical variability. Herein, we describe two affected individuals segregating a recessive NDD. The affected individuals exhibited phenotypes such as global developmental delay (GDD), intellectual disability (ID), microcephaly and speech delay. Whole-exome sequencing (WES) followed by bidirectional Sanger sequencing techniques identified a homozygous nonsense variant (c.466C > T; p.Gln156*) in the PPFIBP1 gene (NM_003622.4) that segregated with the disease phenotype. Further, to elucidate the effect of the variant on protein structure, 3D protein modelling was performed for the mutant and normal protein that suggested substantial reduction of the mutant protein. Our data support the evidence that PPFIBP1 has a pivotal role in neurodevelopment in humans, and loss-of-function variants cause clinically variable neurodevelopmental phenotypes.