title: Clinical and molecular features of adPEO due to mutations in the Twinkle gene.
abstract: We have analyzed Twinkle, the causative gene for autosomal dominant progressive external ophthalmoplegia (adPEO) on chromosome 10, in 11 Australian autosomal dominant progressive external ophthalmoplegia families of Caucasian origin, and investigated whether there are distinct molecular and clinical features associated with mutations in this gene. We found two new mutations in Twinkle, in 3 of the 11 pedigrees examined. One resides in the linker region of this gene while the other is in the primase domain. Both regions are highly conserved between species. Multiple deletions in the mtDNA from muscle are not always prominent and there are significant variations in the clinical presentation within and between families with mutations in the Twinkle gene. Therefore, genotype/phenotype predictions are difficult. No mutations were found in adenine nucleotide translocator 1 (ANT1), another known adPEO causative gene, in four of the seven remaining families investigated. Thus, Twinkle appears to be the most common gene associated with adPEO in Australian families.
authors.affiliation: Murdoch Childrens Research Institute, The Royal Childrens Hospital, Parkville, Victoria 3052, Australia.
authors.forename: Sharon
authors.initials: S
authors.lastname: Lewis
authors.forename: Wendy
authors.initials: W
authors.lastname: Hutchison
authors.forename: Dominic
authors.initials: D
authors.lastname: Thyagarajan
authors.forename: Hans-Henrik M
authors.initials: HH
authors.lastname: Dahl
mesh_terms: D000595:Amino Acid Sequence; D001315:Australia; D002879:Chromosomes, Human, Pair 10; D004265:DNA Helicases; D019915:DNA Primase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation
chemical_list: D024101:Mitochondrial Proteins; D019915:DNA Primase; D004265:DNA Helicases; C431576:TWNK protein, human