caa a22 4500 445808268 CHVBK 20180317145203.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00415-011-5936-x doi (NATIONALLICENCE)springer-10.1007/s00415-011-5936-x Genetic analysis of two Japanese families with progressive external ophthalmoplegia and parkinsonism [Elektronische Daten] [Kazunori Sato, Ichiro Yabe, Hiroaki Yaguchi, Fumihito Nakano, Yasuyuki Kunieda, Shinji Saitoh, Hidenao Sasaki] 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. Springer-Verlag, 2011 Progressive external ophthalmoplegia nationallicence DNA polymerase gamma gene nationallicence Parkinsonism nationallicence Mitochondria nationallicence Sato Kazunori Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut Yabe Ichiro Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut Yaguchi Hiroaki Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut Nakano Fumihito Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut Kunieda Yasuyuki Department of Internal Medicine, Wakkanai City Hospital, Wakkanai, Japan aut Saitoh Shinji Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan aut Sasaki Hidenao Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut Journal of Neurology Springer-Verlag 258/7(2011-07-01), 1327-1332 0340-5354 258:7<1327 2011 258 415 https://doi.org/10.1007/s00415-011-5936-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-011-5936-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sato Kazunori Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut NATIONALLICENCE 700 1- Yabe Ichiro Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut NATIONALLICENCE 700 1- Yaguchi Hiroaki Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut NATIONALLICENCE 700 1- Nakano Fumihito Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut NATIONALLICENCE 700 1- Kunieda Yasuyuki Department of Internal Medicine, Wakkanai City Hospital, Wakkanai, Japan aut NATIONALLICENCE 700 1- Saitoh Shinji Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Sasaki Hidenao Department of Neurology, Hokkaido University Graduate School of Medicine, N15W7, 060-8638, Kita-ku, Japan aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/7(2011-07-01), 1327-1332 0340-5354 258:7<1327 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer