RADX Gene Variant May Predispose to Familial Asperger Syndrome

Asperger syndrome (AS) is a pervasive developmental disorder characterized by general impairment in socialization, stereotypical behavior, defective adaptation to the social context usually without intellectual disability, and some high functioning areas related to memory and mathematics. Clinical criteria are not well defined and the etiology is heterogeneous and mostly unknown. Like in typical autism spectrum disorders (ASD), the genetic background plays a crucial role in AS, and often an almost mendelian segregation can be observed in some families. We performed a whole exome sequencing (WES) in three relatives of a family with vertical transmission of AS-ASD to identify variants in candidate genes segregating with the phenotype. Variant p.(Cys834Ser) in the RADX gene was the only one segregating among all the affected family members. This gene encodes a single-strand DNA binding factor, which mediates the recruitment of genome maintenance proteins to sites of replication stress. Replication stress and genome instability have been reported recently in neural progenitor cells derived from ASD patients, leading to a disruption of long neural genes involved in cell-cell adhesion and migration. We propose RADX as a new gene that when mutated could represent a predisposing factor to AS-ASD.

Automated summary

Asperger syndrome is a pervasive developmental disorder characterized by impaired socialization, stereotypical behavior, and defective social adaptation. Genetic background is important in the development of Asperger syndrome, and a mutation in the RADX gene may play a role as a predisposing factor. The RADX gene encodes a DNA binding factor involved in genome maintenance and its mutation could disrupt neural genes related to cell adhesion and migration.