Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice.

Background: Intellectual developmental disorder with autism and dysmorphic facies (IDDADF) is a rare syndromic intellectual disability (ID) caused by homozygous disruption of PDZD8 (PDZ domain-containing protein 8), an integral endoplasmic reticulum (ER) protein. All four previously identified IDDADF cases exhibit autistic behavior, with autism spectrum disorder (ASD) diagnosed in three cases. To determine whether autistic behavior is a common outcome of PDZD8 disruption, we studied a third family with biallelic mutation of PDZD8 (family C) and further characterized PDZD8-deficient (Pdzd8) mice that exhibit stereotyped motor behavior relevant to ASD.