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

PLoS One. 2021 Oct 15;16(10):e0258766. doi: 10.1371/journal.pone.0258766. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Angelman Syndrome / genetics*
  • Child
  • Exome Sequencing / methods*
  • Female
  • Gene Regulatory Networks*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heat-Shock Proteins
  • Humans
  • Infant
  • Male
  • Matrix Attachment Region Binding Proteins / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Repressor Proteins / genetics
  • Transcription Factors / genetics
  • Vesicle-Associated Membrane Protein 2 / genetics
  • Young Adult

Substances

  • ASXL3 protein, human
  • Heat-Shock Proteins
  • Matrix Attachment Region Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • SATB2 protein, human
  • TBL1XR1 protein, human
  • Transcription Factors
  • VAMP2 protein, human
  • Vesicle-Associated Membrane Protein 2
  • HSF2 protein, human

Grants and funding

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.