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. The present study associated a novel variant in the PPFIBP1 gene that further delineates PPFIBP1‐associated neurodevelopmental disorder. WES revealed a novel homozygous nonsense variant (c.466C > T; p.Gln156*) in the PPFIBP1 gene that segregated perfectly with the disease phenotype and predicted pathogenic referred to various in silico analysis using 3D protein modeling.