New genes involved in Angelman syndrome-like: Expanding the genetic spectrum
Cinthia Aguilera, Elisabeth Gabau, Ariadna Ramírez-Mallafré, Carme Brun i Gasca, Jana Domínguez‐Carral, Verónica Delgadillo, Steven Laurie, Sophia Derdak, Natàlia Padilla, Xavier de la Cruz, Núria Capdevila, Nino Spataro, Neus Baena, Míriam Guitart, Anna Ruiz
Abstract
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.