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Pàgina inicial > Articles > Articles publicats > Identification and characterization of new RNASEH1 mutations associated with PEO syndrome and multiple mitochondrial DNA deletions |
Data: | 2019 |
Resum: | Mitochondrial DNA (mtDNA) depletion and deletion syndrome encompasses a group of disorders caused by mutations in genes involved in mtDNA replication and maintenance. The clinical phenotype ranges from fatal infantile hepatocerebral forms to mild adult onset progressive external ophthalmoplegia (PEO). We report the case of a patient with PEO and multiple mtDNA deletions, with two new homozygous mutations in RNASEH1. The first mutation (c. 487T>C) is located in the same catalytic domain as the four previously reported mutations, and the second (c. 258-260del) is located in the connection domain, where no mutations have been reported. In silico study of the mutations predicted only the first mutation as pathogenic, but functional studies showed that both mutations cause loss of ribonuclease H1 activity. mtDNA replication dysfunction was demonstrated in patient fibroblasts, which were unable to recover normal mtDNA copy number after ethidium bromide-induced mtDNA depletion. Our results demonstrate the pathogenicity of two new RNASEH1 variants found in a patient with PEO syndrome, multiple deletions, and mild mitochondrial myopathy. |
Ajuts: | Ministerio de Economía y Competitividad SAF2017-87506-R Instituto de Salud Carlos III FIS PI1501428 Instituto de Salud Carlos III FIS PI18-01574 Agència de Gestió d'Ajuts Universitaris i de Recerca SLT002-16-00370 |
Nota: | Altres ajuts: This work was supported by the Fondo de Investigaciones Sanitarias and the Generalitat de Catalunya (a grant from the URDCat project PERIS to EG-A and RM). |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Publicat a: | Frontiers in genetics, Vol. 10 Núm. JUN (2019) , p. 576, ISSN 1664-8021 |
8 p, 1.5 MB |