9 documents found, page 1 of 1
Syndromes associated with mitochondrial DNA depletion
Nogueira, Célia; Almeida, Ligia S.; Nesti, C.; Pezzini, I.; Videira, A.; Vilarinh, Laura; Santorelli, F.M.Mitochondrial dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) and, consequently, deficient energy production. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or...
A Novel SUCLA2 Mutation in a Portuguese Child Associated With "Mild" Methylmalo...
Nogueira, Célia; Meschini, M.C.; Nesti, C.; Garcia, P.; Diogo, L.; Valongo, C.; Costa, R.; Videira, A.; Vilarinho, L.; Santorelli, F.M.Succinyl-coenzyme A synthase is a mitochondrial matrix enzyme that catalyzes the reversible synthesis of succinate and adenosine triphosphate (ATP) from succinyl-coenzyme A and adenosine diphosphate (ADP) in the tricarboxylic acid cycle. This enzyme is made up of α and β subunits encoded by SUCLG1 and SUCLA2, respectively. We present a child with severe muscular hypotonia, dystonia, failure to thrive, sensorine...
Identification of maternal uniparental isodisomy of chromosome 10 in a patient ...
Nogueira, Célia; Marques, J.S.; Nesti, C.; Azevedo, A.; Di Lullo, M.; Meschini, M.C.; Orlacchio, A.; Videira, A.; Santorelli, F.M.; Vilarinho, L.Introduction: Twinkle, the mitochondrial helicase encoded by C10orf2, serves a key function in mtDNA replication and its mutations associated with a broad spectrum of clinical conditions characterized by qualitative or quantitative defects of mtDNA, including infantile-onset spinocerebellar ataxia (IOSCA), progressive external ophthalmoplegia, and the hepatocerebral mtDNA depletion syndrome (MDS). The signs in ...
Novel TTC19 mutation in a family with severe psychiatric manifestations and com...
Nogueira, C.; Barros, J.; Sá, M.J.; Azevedo L, L.; Taipa, R.; Torraco, A.; Meschini, M.C.; Verrigni, D.; Nesti, C.; Rizza, T.; Teixeira, João PauloComplex III of the mitochondrial respiratory chain (CIII) catalyzes transfer of electrons from reduced coenzyme Q to cytochrome c. Low biochemical activity of CIII is not a frequent etiology in disorders of oxidative metabolism and is genetically heterogeneous. Recently, mutations in the human tetratricopeptide 19 gene (TTC19) have been involved in the etiology of CIII deficiency through impaired assembly of th...
Novel mutation in the mitochondrial transfer RNACys gene in a child
Almeida, L.S.; Martins, E.; Santorelli, F.M.; Vilarinho, L.Mitochondrial DNA (mtDNA) disorders are an important group of genetic diseases presenting with a multifacet array of clinical manifestations. Highly energy-dependent tissues such as central nervous system and skeletal and cardiac muscles are commonly involved either as multisystem or as isolated organ disease. Characteristic symptoms include epilepsy, myopathy, deafness and ophthalmoplegia, all associated with ...
"Double trouble” or digenic disorder in Complex I deficiency
Almeida, L.S.; Ferreira, M.; Nogueira, C.; Furtado, F.; Evangelista, T.; Santorelli, F.M.; Vilarinho, L.Complex I (CI) deficiency is a defect of OXPHOS caused by mutations in the mitochondrial or nuclear genomes. To date disease-causing mutations have been reported in all mitochondrial-encoded subunits and 22 nuclear genes. In about 50% of the patients no mutations are found, suggesting that undiscovered factors are an important cause of disease. In this study we report a consanguineous family from Southern Portu...
Relative frequency of known causes of multiple mtDNA deletions: two novel POLG ...
Ferreira, M.; Evangelista, T.; Almeida, L.S.; Martins, J.; Macario, M.C.; Martins, E.; Moleirinho, A.; Azevedo, L.; Vilarinho, L.; Santorelli, F.M.Diseases affecting mtDNA stability, termed nuclear–mitochondrial intergenomic communication disorders, are caused by a primary nuclear gene defect resulting in multiple mtDNA deletions. The aim of this study was to estimate the frequency of known etiologies and the spectrum of mutations in a cohort of 21 patients harboring multiple mtDNA deletions in skeletal muscle. We showed that 10 cases (48%) display mutati...
Progressive cavitating leukoencephalopathy associated with respiratory chain co...
Ferreira, M.; Torraco, A.; Rizza, T.; Fattori, F.; Meschini, M.C.; Castana, C.; Go, N.E.; Nargang, F.E.; Duarte, M.; Piemonte, F.; Dionisi-Vici, C.We present clinical, neuroimaging, and molecular data on the identification of a new homozygous c.1783A>G (p.Thr595Ala) mutation in NDUFS1 in two inbred siblings with isolated complex I deficiency associated to a progressive cavitating leukoencephalopathy, a clinical and neuroradiolog- ical entity originally related to unknown defects of the mitochondrial energy metabolism. In both sibs, the muscle biopsy showe...
Molecular investigation of pediatric portuguese patients with sensorineural hea...
Nogueira, C.; Coutinho, M.; Pereira, C.; Tessa, A.; Santorelli, F.M.; Vilarinho, L.The understanding of the molecular genetics in sensorineural hearing loss (SNHL) has advanced rapidly during the last decade, but the molecular etiology of hearing impairment in the Portuguese population has not been investigated thoroughly. To provide appropriate genetic testing and counseling to families, we analyzed the whole mitochondrial genome in 95 unrelated children with SNHL (53 nonsyndromic and 42 syn...