Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations.

TitleNovel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations.
Publication TypeJournal Article
Year of Publication2002
AuthorsCorona, P, Lamantea, E, Greco, M, Carrara, F, Agostino, A, Guidetti, D, Dotti, MT, Mariotti, C, Zeviani, M
JournalAnn Neurol
Volume51
Issue1
Pagination118-22
Date Published2002 Jan
ISSN0364-5134
KeywordsAdult, Amino Acid Substitution, Cardiomyopathies, Deafness, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Electron Transport, Family Health, Female, Humans, Male, Muscle, Skeletal, Muscular Dystrophies, Nucleic Acid Conformation, Paraparesis, Spastic, Pedigree, Point Mutation
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(Ile) 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.

DOI10.1002/ana.10059
Alternate JournalAnn. Neurol.
Citation Key10.1002/ana.10059
PubMed ID11782991