RADX Gene Variant May Predispose to Familial Asperger Syndrome.
Alessia AzzaràRoberto RumoreFulvia BrugnolettiElisabetta TabolacciIrene BottilloEugenio SangiorgiFiorella GurrieriPublished in: Genes (2023)
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.
Keyphrases
- autism spectrum disorder
- intellectual disability
- copy number
- genome wide
- attention deficit hyperactivity disorder
- dna binding
- dna methylation
- cell adhesion
- stem cells
- newly diagnosed
- transcription factor
- end stage renal disease
- working memory
- case report
- mental health
- prognostic factors
- patient reported outcomes
- bone marrow
- genome wide analysis
- drug induced
- cell therapy