TY - JOUR
T1 - Familial Parkinsonism and ophthalmoplegia from a mutation in the mitochondrial DNA helicase twinkle
AU - Baloh, Robert H.
AU - Salavaggione, Ezequiel
AU - Milbrandt, Jeffrey
AU - Pestronk, Alan
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34447249263&partnerID=8YFLogxK
U2 - 10.1001/archneur.64.7.998
DO - 10.1001/archneur.64.7.998
M3 - Article
C2 - 17620490
AN - SCOPUS:34447249263
SN - 0003-9942
VL - 64
SP - 998
EP - 1000
JO - Archives of neurology
JF - Archives of neurology
IS - 7
ER -