Molecular analysis in a family presenting with a mild form of late-onset autosomal dominant chronic progressive external ophthalmoplegia.
Nuclear genes affecting mitochondrial genome stability were screened in an Italian family presenting with autosomal dominant progressive external ophthalmoplegia (adPEO) associated with multiple mitochondrial DNA (mtDNA) deletions. We report on a heterozygous c.907C>T (p.R303W) mutation found in the N-terminal domain of the human mitochondrial DNA helicase, Twinkle protein, in six members of a family, in which two individuals manifested late-onset PEO and morphological and molecular signs of mitochondrial dysfunction along with two carriers who are presently free of disease manifestation. We also investigated if the p.R303W mutation in PEO1 gene affected the relative copy number of mitochondrial DNA genomes.
Department of Medical Biochemistry, Medical Biology and Medical Physics, University of Bari, Bari, Italy.
Roberto
R
Negro
Stefano
S
Zoccolella
Rosa
R
Dell'aglio
Angela
A
Amati
Lucia
L
Artuso
Luigi
L
Bisceglia
Vito
V
Lavolpe
Sergio
S
Papa
Luigi
L
Serlenga
Vittoria
V
Petruzzella
D017668:Age of Onset; D001921:Brain / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005190:Family; D018628:Gene Dosage; D054629:Genome, Mitochondrial; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D017246:Ophthalmoplegia, Chronic Progressive External / Q000097:blood / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human