De Novo Variants in PPFIA2 in Individuals With Neurodevelopmental Disorders.

Abstract

Liprin-α2, encoded by PPFIA2, belongs to the family of Liprin-α proteins which constitute major synaptic scaffolds participating in the assembly and maturation of synapses. Heterozygous de novo variants in PPFIA2 were identified by exome or genome sequencing in two unrelated individuals with a neurodevelopmental disorder. The hypothesis of PPFIA2 as a novel candidate gene for a neurodevelopmental disorder is supported by the gnomAD gene constraint metrics and further strengthened by our identification of seven additional individuals in large cohort studies carrying rare de novo variants and presenting with overlapping phenotype. In summary, we provide evidence for the second gene-disease association of a Liprin-α protein beyond PPFIA3.