New phenotypic diversity associated with the mitochondrial tRNA(SerUCN) gene mutation

We performed detailed clinical, histopathological, biochemical, in vitro translation and molecular genetic analysis in patients from two unrelated families harbouring the tRNA(SerUCN) 7472C-insertion mutation. Proband 1 developed a progressive neurodegenerative phenotype characterised by myoclonus,...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 2005-05, Vol.15 (5), p.364-371
Main Authors: Pulkes, T, Liolitsa, D, Eunson, L H, Rose, M, Nelson, I P, Rahman, S, Poulton, J, Marchington, D R, Landon, D N, Debono, A G, Morgan-Hughes, J A, Hanna, M G
Format: Article
Language:English
Subjects:
Adolescent
Adult
DNA Mutational Analysis - methods
DNA, Mitochondrial - genetics
Electron Transport Complex IV - metabolism
Electrophoresis - methods
Female
Humans
Male
Microscopy, Electron, Transmission - methods
Mitochondria, Muscle - pathology
Mitochondrial Encephalomyopathies - enzymology
Mitochondrial Encephalomyopathies - genetics
Mitochondrial Encephalomyopathies - pathology
Mitochondrial Encephalomyopathies - physiopathology
Mitochondrial Proteins - metabolism
Muscle, Skeletal - enzymology
Muscle, Skeletal - pathology
Muscle, Skeletal - ultrastructure
Mutation
Nucleic Acid Conformation
Phenotype
RNA, Transfer, Ser - chemistry
RNA, Transfer, Ser - genetics
Serine - metabolism
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Summary:We performed detailed clinical, histopathological, biochemical, in vitro translation and molecular genetic analysis in patients from two unrelated families harbouring the tRNA(SerUCN) 7472C-insertion mutation. Proband 1 developed a progressive neurodegenerative phenotype characterised by myoclonus, epilepsy, cerebellar ataxia and progressive hearing loss. Proband 2 had a comparatively benign phenotype characterised by isolated myopathy with exercise intolerance. Both patients had the 7472C-insertion mutation in identical proportions and they exhibited a similar muscle biochemical and histopathological phenotype. However, proband 2 also had a previously unreported homoplasmic A to C transition at nucleotide position 7472 in the tRNA(SerUCN) gene. This change lengthens further the homopolymeric C run already expanded by the 7472C-insertion. These data extend the phenotypic range associated with the 7472C-insertion to include isolated skeletal myopathy, as well as a MERRF-like phenotype.
ISSN:0960-8966
DOI:10.1016/j.nmd.2005.01.006