title: Genetic analysis of two Japanese families with progressive external ophthalmoplegia and parkinsonism.
abstract: Mutations in the progressive external ophthalmoplegia 1 (PEO1), adenine nucleotide translocator 1 (ANT1) and DNA polymerase gamma (POLG) genes were reported in patients with progressive external ophthalmoplegia and parkinsonism. However, the genotype-phenotype correlation and pathophysiology of these syndromes are still unknown. In order to define the molecular basis of progressive external ophthalmoplegia and parkinsonism, we screened for mutations in PEO1, ANT1, POLG genes and the whole mitochondrial genome in two families. In results, we identified a compound heterozygous POLG substitutions, c.830A>T (p.H277L) and c.2827C>T (p.R943C) in one of the families. These two mutations in the coding region of POLG alter conserved amino acids in the exonuclease and polymerase domains, respectively, of the POLG protein. Neither of these substitutions was found in the 100 chromosomes of ethnically matched control subjects. In the other family, no mutations were detected in any of the three genes and the whole mitochondrial genome in the blood sample, although mitochondrial DNA deletions were observed in the muscle biopsy sample. Progressive external ophthalmoplegia and parkinsonism are genetically heterogenous disorders, and part of this syndrome may be caused by mutations in other, unknown genes.
authors.affiliation: Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sato
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yabe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yaguchi
authors.forename: Fumihito
authors.initials: F
authors.lastname: Nakano
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kunieda
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis / Q000379:methods; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D015316:Genetic Therapy; D006801:Humans; D007564:Japan; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications* / Q000235:genetics* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human