OBJECTIVE: To describe the clinical phenotype and genetic basis of a family with autosomal dominant progressive external ophthalmoplegia and parkinsonism from a Twinkle mutation. DESIGN: All coding exons of POLG1, Twinkle (aka C10ORF2, PEO1), and ANT1 (SLC25A4) were sequenced in the proband with targeted sequencing of the Twinkle gene in all additional subjects. SUBJECTS: Members of a 3-generation family followed up in a neuromuscular disease center for dominantly inherited progressive external ophthalmoplegia. RESULTS: We identified a heterozygous G1121A mutation (R374Q) in exon 1 of Twinkle that segregated with the disease phenotype in all affected family members. No pathogenic mutations were present in POLG1 or ANT1. CONCLUSION: This finding broadens the clinical spectrum of Twinkle gene mutations and further implicates loss of mitochondrial DNA integrity in the pathogenesis of Parkinson disease.
OBJECTIVE: To describe the clinical phenotype and genetic basis of a family with autosomal dominant progressive external ophthalmoplegia and parkinsonism from a Twinkle mutation. DESIGN: All coding exons of POLG1, Twinkle (aka C10ORF2, PEO1), and ANT1 (SLC25A4) were sequenced in the proband with targeted sequencing of the Twinkle gene in all additional subjects. SUBJECTS: Members of a 3-generation family followed up in a neuromuscular disease center for dominantly inherited progressive external ophthalmoplegia. RESULTS: We identified a heterozygous G1121A mutation (R374Q) in exon 1 of Twinkle that segregated with the disease phenotype in all affected family members. No pathogenic mutations were present in POLG1 or ANT1. CONCLUSION: This finding broadens the clinical spectrum of Twinkle gene mutations and further implicates loss of mitochondrial DNA integrity in the pathogenesis of Parkinson disease.
Authors: Der-Fen Suen; Derek P Narendra; Atsushi Tanaka; Giovanni Manfredi; Richard J Youle Journal: Proc Natl Acad Sci U S A Date: 2010-06-14 Impact factor: 11.205
Authors: Katarzyna Gaweda-Walerych; Aleksandra Maruszak; Krzysztof Safranow; Monika Bialecka; Gabriela Klodowska-Duda; Krzysztof Czyzewski; Jaroslaw Slawek; Monika Rudzinska; Maria Styczynska; Grzegorz Opala; Marek Drozdzik; Jeffrey A Canter; Maria Barcikowska; Cezary Zekanowski Journal: J Neural Transm (Vienna) Date: 2008-09-23 Impact factor: 3.575
Authors: Derek P Narendra; Seok Min Jin; Atsushi Tanaka; Der-Fen Suen; Clement A Gautier; Jie Shen; Mark R Cookson; Richard J Youle Journal: PLoS Biol Date: 2010-01-26 Impact factor: 8.029