例如:"lncRNA", "apoptosis", "WRKY"

A Novel WAC Loss of Function Mutation in an Individual Presenting with Encephalopathy Related to Status Epilepticus during Sleep (ESES).

Genes (Basel). 2020 Mar 24;11(3)
Emanuela Leonardi 1 , Mariagrazia Bellini 1 , Maria C Aspromonte 1 , Roberta Polli 1 , Anna Mercante 2 , Claudia Ciaccio 3 , Elisa Granocchio 3 , Elisa Bettella 1 , Ilaria Donati 4 , Elisa Cainelli 5 , Stefania Boni 6 , Stefano Sartori 2 , Chiara Pantaleoni 3 , Clementina Boniver 2 , Alessandra Murgia 1
Emanuela Leonardi 1 , Mariagrazia Bellini 1 , Maria C Aspromonte 1 , Roberta Polli 1 , Anna Mercante 2 , Claudia Ciaccio 3 , Elisa Granocchio 3 , Elisa Bettella 1 , Ilaria Donati 4 , Elisa Cainelli 5 , Stefania Boni 6 , Stefano Sartori 2 , Chiara Pantaleoni 3 , Clementina Boniver 2 , Alessandra Murgia 1
+ et al

[No authors listed]

Author information
  • 1 Fondazione Istituto di Ricerca Pediatrica (IRP), Città della Speranza, 35127 Padova, Italy.
  • 2 Pediatric Neurology and Neurophysiology Unit, Department of Women's and Children's Health, University l of Padova, 35128 Padua, Italy.
  • 3 Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.
  • 4 Unit of Medical Genetics, AUSL Romagna, 47522 Cesena, Italy.
  • 5 Department of Medical Sciences, University of Ferrara, 44100 Ferrara, Italy.
  • 6 Medical Genetics Unit, S. Martino Hospital, 32100 Belluno, Italy.

摘要


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.

KEYWORDS: ASD, ESES, ID, NGS, WAC, epilepsy, gene panel, mosaicism