New genes involved in Angelman syndrome-like: Expanding the genetic spectrum

Angelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with absence of speech, happy disposition, frequent laughter, hyperactivity, stereotypies, ataxia and seizures with specific EEG abnormalities. There is a 10–15% of patients with an AS phenotype whose genetic cause remains unknown (Angelman-like syndrome, AS-like). Whole-exome sequencing (WES) was performed on a cohort of 14 patients with clinical features of AS and no molecular diagnosis. As a result, we identified 10 de novo and 1 X-linked pathogenic/likely pathogenic variants in 10 neurodevelopmental genes ( SYNGAP1 , VAMP2 , TBL1XR1 , ASXL3 , SATB2 , SMARCE1 , SPTAN1 , KCNQ3 , SLC6A1 and LAS1L ) and one deleterious de novo variant in a candidate gene ( HSF2 ). Our results highlight the wide genetic heterogeneity in AS-like patients and expands the differential diagnosis.