Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions.
Progressive external ophthalmoplegias (PEO) characterized by accumulation of large-scale mitochondrial DNA (mtDNA) deletions are rare human diseases. We mapped a new locus for dominant PEO at 15q22-q26 in a Belgian pedigree and identified a heterozygous mutation (Y955C) in the polymerase motif B of the mtDNA polymerase gamma (POLG). We identified three additional POLG missense mutations compatible with recessive PEO In two nuclear families. POLG is the only DNA polymerase responsible for mtDNA replication.
Van Goethem
G
G
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, University of Antwerp, Universiteitsplein 1; B-2610 Antwerpen, Belgium.
Dermaut
B
B
Löfgren
A
A
Martin
J J
JJ
Van Broeckhoven
C
C
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001530:Belgium; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D017246:Ophthalmoplegia, Chronic Progressive External / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human