TY - JOUR
T1 - A novel WAC loss of function mutation in an individual presenting with encephalopathy related to status epilepticus during sleep (ESES)
AU - Leonardi, Emanuela
AU - Bellini, Mariagrazia
AU - Aspromonte, Maria C.
AU - Polli, Roberta
AU - Mercante, Anna
AU - Ciaccio, Claudia
AU - Granocchio, Elisa
AU - Bettella, Elisa
AU - Donati, Ilaria
AU - Cainelli, Elisa
AU - Boni, Stefania
AU - Sartori, Stefano
AU - Pantaleoni, Chiara
AU - Boniver, Clementina
AU - Murgia, Alessandra
N1 - Funding Information:
Funding: This work was supported by the Italian Ministry of Health Young Investigator (Grant GR-2011-02347754) and Fondazione Istituto di Ricerca Pediatrica–Città della Speranza (Grant 18-04 to E.L and 19/12 to Alessandra Murgia).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - ASD
KW - Epilepsy
KW - ESES
KW - Gene panel
KW - ID
KW - Mosaicism
KW - NGS
KW - WAC
UR - http://www.scopus.com/inward/record.url?scp=85082481693&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082481693&partnerID=8YFLogxK
U2 - 10.3390/genes11030344
DO - 10.3390/genes11030344
M3 - Article
C2 - 32214004
AN - SCOPUS:85082481693
VL - 11
JO - Genes
JF - Genes
SN - 2073-4425
IS - 3
M1 - 344
ER -