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GNAO1 encephalopathy : further delineation of a severe neurodevelopmental syndrome affecting females
Marcé-Grau, Anna (Vall d'Hebron Hospitals. Institut de Recerca)
Dalton, James A.R. (Universitat Autònoma de Barcelona. Institut de Neurociències)
López-Pisón, Javier (Sección de Neuropediatría, Hospital Universitario Miguel Servet)
García-Jiménez, María Concepción (Sección de Metabolismo, Hospital Universitario Miguel Servet)
Monge-Galindo, Lorena (Secciones de Neuropediatría y Metabolismo, Hospital Universitario Miguel Servet)
Cuenca-León, Ester (Vall d'Hebron Hospitals. Institut de Recerca)
Giraldo, Jesús (Universitat Autònoma de Barcelona. Institut de Neurociències)
Macaya, Alfons (Pediatric Neurology Section, Hospital Universitari Vall d'Hebron)

Date: 2016
Abstract: De novo heterozygous mutations in the GNAO1 gene, encoding the Gα o subunit of G-proteins, are the cause of a severe neurodevelopmental disorder, featuring early infantile seizures, profound cognitive dysfunction and, occasionally, movement disorder (early infantile epileptic encephalopathy-17). We report a further case of this association in a 20 month-old Spanish girl with neonatal-onset refractory seizures, progressive microcephaly, oral-lingual dyskinesia and nearly absent psychomotor development. We performed whole-exome sequencing, a computational structural analysis of the novel gene variant identified and reviewed the previously reported cases. Trio whole-exome-sequencing uncovered a de novo p. Leu199Pro GNAO1 mutation. Computational structural analysis indicates this novel variant adversely affects the stability of the G-protein heterotrimeric complex as a whole. Of note, our patient showed a sustained seizure reduction while on a ketogenic diet. With this observation, a total of twelve patients with GNAO1 encephalopathy have been reported. Oral-lingual dyskinesia and responsiveness of seizures to ketogenic diet are novel features. The distorted sex ratio (12/12 females) of the condition remains unexplained; a differential gender effect of the disruption of G-protein- mediated signal transduction on the developing brain can be hypothesized. The online version of this article (doi:10. 1186/s13023-016-0416-0) contains supplementary material, which is available to authorized users.
Note: Número d'acord de subvenció ISCIII/PI12/01005
Note: Número d'acord de subvenció MINECO/SAF2014-58396-R
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Early infantile epileptic encephalopathy ; GNAO1 ; Exome sequencing ; Ketogenic diet
Published in: Orphanet Journal of Rare Diseases, Vol. 11 (april 2016) , ISSN 1750-1172

PMID: 27072799
DOI: 10.1186/s13023-016-0416-0

9 p, 2.9 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2018-02-07, last modified 2019-02-04

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