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

Síndrome de Angelman; Fenotipo Síndrome d'Angelman; Fenotip Angelman syndrome; Phenotype 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. This work is supported by Instituto de Salud Carlos III (MG, PI16/01411), Asociación Española de Síndrome de Angelman (EG), Institut d’investigació i innovació Parc Taulí I3PT (CA, CIR2016/025, CIR2018/021) and Ministerio de Economía y Competitividad (XD, SAF2016-14 80255-R). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.