000070618 001__ 70618
000070618 005__ 20200221144328.0
000070618 0247_ $$2doi$$a10.1186/s13023-016-0416-0
000070618 0248_ $$2sideral$$a106074
000070618 037__ $$aART-2016-106074
000070618 041__ $$aeng
000070618 100__ $$aMarce-Grau, A.
000070618 245__ $$aGNAO1 encephalopathy: further delineation of a severe neurodevelopmental syndrome affecting females
000070618 260__ $$c2016
000070618 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070618 5203_ $$aBackground: 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.
000070618 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI12-01005$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2014-58396-R
000070618 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000070618 590__ $$a3.507$$b2016
000070618 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b35 / 128 = 0.273$$c2016$$dQ2$$eT1
000070618 591__ $$aGENETICS & HEREDITY$$b58 / 166 = 0.349$$c2016$$dQ2$$eT2
000070618 592__ $$a1.57$$b2016
000070618 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000070618 593__ $$aPharmacology (medical)$$c2016$$dQ1
000070618 593__ $$aGenetics (clinical)$$c2016$$dQ2
000070618 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070618 700__ $$aDalton, J.
000070618 700__ $$aLopez-Pison, J.
000070618 700__ $$0(orcid)0000-0002-5563-3177$$aGarcia-Jimenez, M.C.$$uUniversidad de Zaragoza
000070618 700__ $$aMonge-Galindo, L.
000070618 700__ $$aCuenca-Leon, E.
000070618 700__ $$aGiraldo, J.
000070618 700__ $$aMacaya, A.
000070618 7102_ $$11010$$2670$$aUniversidad de Zaragoza$$bDpto. Pediatría Radiol.Med.Fís$$cÁrea Pediatría
000070618 773__ $$g11 (2016), 38 [9 pp]$$pOrphanet Journal of Rare Diseases$$tOrphanet Journal of Rare Diseases$$x1750-1172
000070618 8564_ $$s3025408$$uhttps://zaguan.unizar.es/record/70618/files/texto_completo.pdf$$yVersión publicada
000070618 8564_ $$s105801$$uhttps://zaguan.unizar.es/record/70618/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070618 909CO $$ooai:zaguan.unizar.es:70618$$particulos$$pdriver
000070618 951__ $$a2020-02-21-13:44:57
000070618 980__ $$aARTICLE