A novel WAC loss of function mutation in an individual presenting with encephalopathy related to status epilepticus during sleep (ESES)

Emanuela Leonardi, Mariagrazia Bellini, Maria C. Aspromonte, Roberta Polli, Anna Mercante, Claudia Ciaccio, Elisa Granocchio, Elisa Bettella, Ilaria Donati, Elisa Cainelli, Stefania Boni, Stefano Sartori, Chiara Pantaleoni, Clementina Boniver, Alessandra Murgia

Research output: Contribution to journalArticlepeer-review

Abstract

WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five WAC rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C>A (p.Ser125*); and a novel c.381+2T>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another WAC individual. This first report of a WAC somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with WAC pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders.

Original languageEnglish
Article number344
JournalGenes
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2020

Keywords

  • ASD
  • Epilepsy
  • ESES
  • Gene panel
  • ID
  • Mosaicism
  • NGS
  • WAC

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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