TY - JOUR
T1 - An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region
AU - Zeviani, Massimo
AU - Servidei, Serenella
AU - Gellera, Cinzia
AU - Bertini, Enrico
AU - DiMauro, Salvatore
AU - DiDonato, Stefano
PY - 1989
Y1 - 1989
N2 - DELETIONS of muscle mitochondrial DNA (mtDNA) have recently been found in patients with mitochondrial myopathy1-3. However, as most of the described cases were sporadic, and individual deletions involved different portions of mtDNA1,2, the mechanism(s) producing the molecular lesions, as well as their mode of transmission, remain unclear. By studying families with mtDNA heteroplasmy4, valuable information can be obtained about the role of inheritable factors in the pathogenesis of these disorders. We have studied four members of a family with autosomal dominant mitochondrial myopathy. Multiple deletions, involving the same portion of muscle mtDNA, were identified in all patients. Sequence analysis of the mutant mtDNAs, performed after DNA amplification by the polymerase-chain reaction showed that all the deletions start within a 12-nucleotide stretch at the 5′ end of the D-loop region, a site of active communication between the nucleus and the mtDNA. The data indicate that a mutation of a nuclear-coded protein can destroy the integrity of the mitochondrial genome in a specific, heritable way.
AB - DELETIONS of muscle mitochondrial DNA (mtDNA) have recently been found in patients with mitochondrial myopathy1-3. However, as most of the described cases were sporadic, and individual deletions involved different portions of mtDNA1,2, the mechanism(s) producing the molecular lesions, as well as their mode of transmission, remain unclear. By studying families with mtDNA heteroplasmy4, valuable information can be obtained about the role of inheritable factors in the pathogenesis of these disorders. We have studied four members of a family with autosomal dominant mitochondrial myopathy. Multiple deletions, involving the same portion of muscle mtDNA, were identified in all patients. Sequence analysis of the mutant mtDNAs, performed after DNA amplification by the polymerase-chain reaction showed that all the deletions start within a 12-nucleotide stretch at the 5′ end of the D-loop region, a site of active communication between the nucleus and the mtDNA. The data indicate that a mutation of a nuclear-coded protein can destroy the integrity of the mitochondrial genome in a specific, heritable way.
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M3 - Article
C2 - 2725645
AN - SCOPUS:0024601360
VL - 339
SP - 309
EP - 311
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6222
ER -