title: Rapidly progressive neurodegeneration in a case with the 7472insC mutation and the A7472C polymorphism in the mtDNA tRNA ser(UCN) gene.
abstract: The authors report the clinical, neuroimaging, muscle biopsy and mtDNA findings in a patient affected by bilateral hearing loss and mental retardation since infancy, presenting at age 31 years with a rapid deterioration of mental status and ataxia leading to vegetative condition and death at the age of 32 years. Clinical and genetic studies have been also performed in the mother, affected by neurosensorial hearing loss. Muscle biopsy showed severe mitochondrial alterations in the propositus and evidence of mitochondrial alterations in his mother. Direct mtDNA sequencing in all family members revealed the known 7472insC mutation and the recently described A7472C sequence variation in the tRNA(Ser(UCN))gene. RFLP-PCR confirmed the heteroplasmic nature of the two mutations and failed to find the second transversion in 200 controls. The percentage of mutant genomes harbouring 7472insC ranged from 3 to 7% in asymptomatic family members to 70% in the proband and his mother, whereas the percentage of A7472C mutant genomes was about 90% in all maternal relatives except the proband (56%) and his sister (5%). In conclusion, this is the first report of a rapidly progressive encephalopathy in association with the 7472insC mutation in mtDNA, combined with an A>C variation at the same nucleotide with a possible suppression effect on the pathogenic mutation.
authors.affiliation: Department of Neurological and Behavioural Sciences, Medical School, University of Siena, Viale Bracci 2, 53100 Siena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cardaioli
authors.forename: Paola
authors.initials: P
authors.lastname: Da Pozzo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cerase
authors.forename: Francesco
authors.initials: F
authors.lastname: Sicurelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Malandrini
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Stromillo
authors.forename: Carla
authors.initials: C
authors.lastname: Battisti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Antonio
authors.initials: A
authors.lastname: Federico
mesh_terms: D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009132:Muscles / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012362:RNA, Transfer, Ser / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D012362:RNA, Transfer, Ser; D003545:Cysteine