000086509 001__ 86509
000086509 005__ 20210212121620.0
000086509 0247_ $$2doi$$a10.1016/j.ymgme.2019.01.001
000086509 0248_ $$2sideral$$a110429
000086509 037__ $$aART-2019-110429
000086509 041__ $$aeng
000086509 100__ $$aBaide-Mairena, H.
000086509 245__ $$aMutations in the mitochondrial complex I assembly factor NDUFAF6 cause isolated bilateral striatal necrosis and progressive dystonia in childhood
000086509 260__ $$c2019
000086509 5060_ $$aAccess copy available to the general public$$fUnrestricted
000086509 5203_ $$aAim: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations. Method: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts. Results: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Brain magnetic resonance showed symmetric and bilateral cytotoxic lesions in the putamen and proliferation of the lenticular-striate arteries, latter spreading to the caudate and progressing to cavitation and volume loss. We identified a frameshift novel change (c.554_558delTTCTT; p.Tyr187AsnfsTer65) and a pathogenic missense change (c.371T>C; p.Ile124Thr) in the NDUFAF6 gene, which segregated with an autosomal recessive inheritance within the family. Patient mutations were associated with the absence of the NDUFAF6 protein and reduced activity and assembly of mature complex I in fibroblasts. By functional complementation assay, the mutant phenotype was rescued by the canonical version of the NDUFAF6. A literature review of 14 NDUFAF6 patients showed a consistent phenotype of an early childhood insidious onset neurological regression with prominent dystonia associated with basal ganglia degeneration and long survival. Interpretation: NDUFAF6-related Leigh syndrome is a relevant cause of childhood onset dystonia and isolated bilateral striatal necrosis. By genetic complementation, we could demonstrate the pathogenicity of novel genetic variants in NDUFAF6.
000086509 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI15-00287$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS/PI18-01319$$9info:eu-repo/grantAgreement/ES/ISCIII/PI17-00021$$9info:eu-repo/grantAgreement/ES/MICINN-ISCIII-ERDF/RETICS-RD12-0005
000086509 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000086509 590__ $$a4.17$$b2019
000086509 591__ $$aENDOCRINOLOGY & METABOLISM$$b35 / 143 = 0.245$$c2019$$dQ1$$eT1
000086509 591__ $$aGENETICS & HEREDITY$$b42 / 177 = 0.237$$c2019$$dQ1$$eT1
000086509 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b43 / 138 = 0.312$$c2019$$dQ2$$eT1
000086509 592__ $$a1.404$$b2019
000086509 593__ $$aBiochemistry$$c2019$$dQ1
000086509 593__ $$aEndocrinology$$c2019$$dQ1
000086509 593__ $$aEndocrinology, Diabetes and Metabolism$$c2019$$dQ1
000086509 593__ $$aGenetics$$c2019$$dQ2
000086509 593__ $$aMolecular Biology$$c2019$$dQ2
000086509 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000086509 700__ $$0(orcid)0000-0002-9779-8826$$aGaudó, P.$$uUniversidad de Zaragoza
000086509 700__ $$aMarti-Sánchez, L.
000086509 700__ $$0(orcid)0000-0001-5964-6138$$aEmperador, S.$$uUniversidad de Zaragoza
000086509 700__ $$aSánchez-Montanez, A.
000086509 700__ $$aAlonso-Luengo, O.
000086509 700__ $$aCorrea, M.
000086509 700__ $$aGrau, A.M.
000086509 700__ $$aOrtigoza-Escobar, J.D.
000086509 700__ $$aArtuch, R.
000086509 700__ $$aVázquez, E.
000086509 700__ $$aDel Toro, M.
000086509 700__ $$0(orcid)0000-0003-0145-3020$$aGarrido-Pérez, N.$$uUniversidad de Zaragoza
000086509 700__ $$aRuiz-Pesini, E.
000086509 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya, J.$$uUniversidad de Zaragoza
000086509 700__ $$0(orcid)0000-0002-8585-6371$$aBayona-Bafaluy, M.P.$$uUniversidad de Zaragoza
000086509 700__ $$aPérez-Dueñas, B.
000086509 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología
000086509 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000086509 773__ $$g126, 3 (2019), 250-258$$pMol. genet. metab.$$tMolecular Genetics and Metabolism$$x1096-7192
000086509 8564_ $$s473763$$uhttps://zaguan.unizar.es/record/86509/files/texto_completo.pdf$$yPostprint
000086509 8564_ $$s49326$$uhttps://zaguan.unizar.es/record/86509/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000086509 909CO $$ooai:zaguan.unizar.es:86509$$particulos$$pdriver
000086509 951__ $$a2021-02-12-12:06:13
000086509 980__ $$aARTICLE