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Autosomal Recessive Cerebellar Ataxia and Low Mitocondrial Complex III in a Portuguese Family

2012-11Conference object Open access
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dc.contributor.authorNogueira, Célia
dc.contributor.authorNesti, Claudia
dc.contributor.authorMeschini, Maria Chiara
dc.contributor.authorCarrozzo, Rosalba
dc.contributor.authorBarros, Jose
dc.contributor.authorSá, Maria José
dc.contributor.authorAzevedo, Luisa
dc.contributor.authorVilarinho, Laura
dc.contributor.authorSantorelli, Filippo
dc.date.accessioned2013-02-06T18:05:09Z
dc.date.available2013-02-06T18:05:09Z
dc.date.issued2012-11
dc.descriptionPublicado em: Livro de abstracts do congresso LIMPE_DISMOV 2012por
dc.description.abstractIntroduction: Defects of mitochondrial complex III (CIII) are a relatively rare cause of mitochondrial dysfunction. The complex catalyzes the electron transfer from reduced coenzyme Q to cytochrome c and is composed of 11 subunits, one of which (MT-CYB) is mtDNA encoded. Mutations in MT-CYB and in assembly factor BCS1L account for the vast majority of cases with low CIII, and are associated with a wide range of neurological disorders. The gene coding for human tetratricopeptide 19 (TTC19) produces a poorly characterized protein thought to be involved in the correct assembly of CIII. Recently, mutations in TTC19 have been described in three unrelated Italian kindred in association with a severe neurodegenerative disease. Objectives: We studied a consanguineous Portuguese family where a severe neurometabolic disorder occurred in four siblings (three men and one woman) in association with a slowly progressive disorder characterized by dystonia of hands and feet, ataxic gait, severe olivo-ponto-cerebellar atrophy documented at brain MRI, and relentless psychiatric manifestations. Variability in age at onset and disease course was observed. Methods: The enzymatic activity of CIII was determined in muscle using a reported spectrophotometric method. Sequence analysis of genomic DNA was performed to identify disease-causing mutations in TTC19. Immunodetection analysis in muscle homogenate and skin fibroblasts allowed the detection of the amount TTC19 protein using a commercially available anti-TTC19 antibody. Results: In this family, we identified a novel homozygous TTC19 mutation predicting frameshift and early protein truncation. The mutation was heterozygous in parents and healthy siblings, and it was absent in ethnically-matched controls. The protein was undetectable in tissues by Western blot analyses. Conclusion: This is the fourth kindred presenting mutations in TTC19. The clinical phenotype of such condition is severe, embraces neurological and psychiatric symptoms, and represents a further example of autosomal recessive ataxia of metabolic origin.por
dc.identifier.urihttp://hdl.handle.net/10400.18/1194
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherLIMPE_DISMOVpor
dc.subjectCIIIpor
dc.subjectAtaxiapor
dc.subjectDoenças Genéticaspor
dc.titleAutosomal Recessive Cerebellar Ataxia and Low Mitocondrial Complex III in a Portuguese Familypor
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlacePisa, Itálapor
oaire.citation.titleCongresso Congiunto LIMPE/DISMOV-SIN, 7-10 Novembre 2012por
rcaap.rightsopenAccesspor
rcaap.typeconferenceObjectpor

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