Epigenetic Signatures in Family Clusters: Links Between Male Fertility and Autism Risk.

Autism spectrum disorder (ASD) prevalence has increased globally. Emerging evidence implicates paternal genetic and epigenetic factors, particularly sperm DNA methylation alterations, in shaping offspring neurodevelopmental risk. Advanced paternal age is associated with increased de novo mutations and epigenetic changes in germ cells. Recent studies have explored distinct sperm methylation signatures in fathers of autistic children, often involving genes critical for neural signaling, transcription, and synaptic function. Longitudinal analyses further linked paternal sperm methylation patterns-including WWOX, SALL3, and A2BP1 (RBFOX1)-with autistic traits in both fathers and their children, supporting intergenerational epigenetic transmission of ASD susceptibility.