Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations

P. Corona, E. Lamantea, M. Greco, F. Carrara, A. Agostino, D. Guidetti, M. T. Dotti, C. Mariotti, M. Zeviani

Research output: Contribution to journalArticle

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Abstract

The protean manifestations of a novel maternally inherited point mutation of the mitochondrial genome are reported. The proband showed isolated, spastic paraparesis. A brother, who had suffered from a multisystem progressive disorder, ultimately died of cardiomyopathy. Another brother is healthy. The proband's mother showed truncal ataxia, dysarthria, severe hearing loss, mental regression, ptosis, ophthalmoparesis, distal cyclones, and diabetes mellitus. A muscle biopsy performed in the proband failed to show the morphological abnormalities typical of mitochondrial disorders; the activities of respiratory chain complexes were normal. However, complex I and IV activities were low in the muscle homogenate of the affected mother and brother. Sequence analysis of mtDNA showed a heteroplasmic mutation of the tRNA I1e gene (G4284A). The mutation load was approximately 55%, 80%, and 90% in the muscle mtDNA of the proband, his mother, and his affected brother, respectively. Mutation was undetected in the healthy brother, as well as in 100 control samples. Several cybrid clones containing homoplasmic mutant mtDNA from the proband showed significant reductions of complex IV activity and maximum oxygen consumption rate, compared with homoplasmic wild-type clones derived from the same subject.

Original languageEnglish
Pages (from-to)118-122
Number of pages5
JournalAnnals of Neurology
Volume51
Issue number1
DOIs
Publication statusPublished - 2002

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Mitochondrial DNA
Muscles
Mutation
Clone Cells
Spastic Paraparesis
Cyclonic Storms
Ophthalmoplegia
Mitochondrial Diseases
Dysarthria
Mitochondrial Genome
Ataxia
Electron Transport
Transfer RNA
Cardiomyopathies
Hearing Loss
Point Mutation
Oxygen Consumption
Sequence Analysis
Diabetes Mellitus
Biopsy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Corona, P., Lamantea, E., Greco, M., Carrara, F., Agostino, A., Guidetti, D., ... Zeviani, M. (2002). Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. Annals of Neurology, 51(1), 118-122. https://doi.org/10.1002/ana.10059

Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. / Corona, P.; Lamantea, E.; Greco, M.; Carrara, F.; Agostino, A.; Guidetti, D.; Dotti, M. T.; Mariotti, C.; Zeviani, M.

In: Annals of Neurology, Vol. 51, No. 1, 2002, p. 118-122.

Research output: Contribution to journalArticle

Corona, P, Lamantea, E, Greco, M, Carrara, F, Agostino, A, Guidetti, D, Dotti, MT, Mariotti, C & Zeviani, M 2002, 'Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations', Annals of Neurology, vol. 51, no. 1, pp. 118-122. https://doi.org/10.1002/ana.10059
Corona, P. ; Lamantea, E. ; Greco, M. ; Carrara, F. ; Agostino, A. ; Guidetti, D. ; Dotti, M. T. ; Mariotti, C. ; Zeviani, M. / Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. In: Annals of Neurology. 2002 ; Vol. 51, No. 1. pp. 118-122.
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