title: Clinical variability in maternally inherited leber hereditary optic neuropathy with the G14459A mutation.
abstract: Spasticity and dystonia have been associated with mitochondrial (mt) DNA mutations at A11696G, G14459A, and T14596A. We describe the clinical features and molecular analysis of two Caucasian pedigrees with the 14,459 guanosine (G) --> adenine (A) transition. The maternally inherited Leber hereditary optic neuropathy (LHON) phenotypes showed extreme clinical variability and the only screening test that was abnormal in the patient with spasticity/dystonia was a high T2 signal in the putamen bilaterally. The male patient in the second pedigree showed features of optic neuropathy without spasticity/dystonia. These results further support that the 14,459 G --> A transition mutation is causally related to LHON and spasticity/dystonia.
authors.affiliation: Department of Neurology, 4U4, McMaster University, 1200 Main Street W., Hamilton, Ontario, Canada L8N 3Z5. tarnopol@mcmaster.ca
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.forename: Steven K
authors.initials: SK
authors.lastname: Baker
authors.forename: Tomoko
authors.initials: T
authors.lastname: Myint
authors.forename: C E
authors.initials: CE
authors.lastname: Maxner
authors.forename: J
authors.initials: J
authors.lastname: Robitaille
authors.forename: Brian H
authors.initials: BH
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D004421:Dystonia / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009128:Muscle Spasticity / Q000175:diagnosis* / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis* / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D011699:Putamen / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial