GNAO1 encephalopathy: further delineation of a severe neurodevelopmental syndrome affecting females

Marce-Grau, A. ; Dalton, J. ; Lopez-Pison, J. ; Garcia-Jimenez, M.C. (Universidad de Zaragoza) ; Monge-Galindo, L. ; Cuenca-Leon, E. ; Giraldo, J. ; Macaya, A.

Resumen: Background: De novo heterozygous mutations in the GNAO1 gene, encoding the Ga 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). Methods: 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. Results: 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. Conclusions: 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.

Idioma: Inglés

DOI: 10.1186/s13023-016-0416-0

Año: 2016

Publicado en: Orphanet Journal of Rare Diseases 11 (2016), 38 [9 pp]
ISSN: 1750-1172

Factor impacto JCR: 3.507 (2016)

Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 35 / 128 = 0.273 (2016) - Q2 - T1
Categ. JCR: GENETICS & HEREDITY rank: 58 / 166 = 0.349 (2016) - Q2 - T2

Factor impacto SCIMAGO: 1.57 - Medicine (miscellaneous) (Q1) - Pharmacology (medical) (Q1) - Genetics (clinical) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/PI12-01005
Financiación: info:eu-repo/grantAgreement/ES/MINECO/SAF2014-58396-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Pediatría (Dpto. Pediatría Radiol.Med.Fís)