Recurrent GNAO1 Mutations Associated With Developmental Delay and a Movement Disorder.
In 2 unrelated patients with axial hypotonia, developmental delay and a hyperkinetic movement disorder, a missense mutation was found in codon 209 of the GNAO1 gene. From the still scarce literature on GNAO1 mutations, a clear genotype-phenotype correlation emerged. From the 26 patients reported thus far, 12 patients had epileptic encephalopathy, and 14 had a developmental delay and a hyperkinetic movement disorder. All but 1 of the latter patients had missense mutations in GNAO1 codon 209 or 246, which thus appear to be mutation hotspots. At least 2 sibling pairs showed that the recurrence risk after 1 affected child with a GNAO1 mutation might be relatively high (5-15%), due to apparent gonadal mosaicism in the parents.
Department of Pediatrics, Academic Medical Center, Amsterdam, the Netherlands.
Leonie A
LA
Menke
Department of Pediatric Neurology, Academic Medical Center, Amsterdam, the Netherlands.
Marc
M
Engelen
Department of Medical Genetics, Academic Medical Center, Amsterdam, the Netherlands.
Mariel
M
Alders
Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands.
Vincent J J
VJ
Odekerken
Department of Pediatric Neurology, Academic Medical Center, Amsterdam, the Netherlands.
Frank
F
Baas
Department of Pediatrics, Academic Medical Center, Amsterdam, the Netherlands j.m.cobben@amc.uva.nl jan.cobben@stgeorges.nhs.uk.|Department of Clinical Genetics, St George's University Hospital, London, UK.
Jan M
JM
Cobben
D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics* / Q000503:physiopathology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009069:Movement Disorders / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D035781:Siblings
C584143:GNAO1 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go

GNAO1
; chorea; developmental delay; dystonia; epileptic encephalopathy