A SWI/SNF related autism syndrome caused by de novo mutations in ADNP

摘要

Despite a high heritability, a genetic diagnosis can only be established in a minority of patients with autism spectrum disorder (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, such as the Rett and Fragile X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next generation sequencing, for the large majority of cases no molecular diagnosis can be established ^-. Here, we report 10 patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD genes known to date.