Parkinson disease: analysis of mitochondrial DNA in monozygotic twins.
We have sequenced all mitochondrial complex I and tRNA genes in five pairs of monozygotic twins with a longitudinal diagnosis of idiopathic Parkinson disease (PD). At the time of molecular genetic analysis, four of the pairs were discordant for PD. Five novel homoplasmic sequence variants, including two missense mutations (ND2 4924 G/A, ND3 10192 C/T), were detected in mitochondrial genes of complex I in four of the pairs. In addition, a total of 20 known polymorphisms affecting both complex I and tRNA genes was found. Importantly, mitochondrial DNA sequences were identical in diseased and non-affected siblings of each pair. Our results demonstrate that missense mutations of mitochondrial complex I may occur in clinically discordant parkinsonian twins, questioning the direct pathogenic relevance of at least some of these mutations.
Kösel
S
S
Labor für Molekulare Neuropathologie, Institut für Neuropathologie, Ludwig-Maximilians-Universität, Munich, Germany.
Grasbon-Frodl
E M
EM
Hagenah
J M
JM
Graeber
M B
MB
Vieregge
P
P
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D021122:Protein Subunits; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014430:Twins, Monozygotic
D004272:DNA, Mitochondrial; D021122:Protein Subunits; D016660:NAD(P)H Dehydrogenase (Quinone)