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

• Published in: Neuromuscular disorders : NMD Vol. 15; no. 5; pp. 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: Journal Article
• Language: English
• Published: England 01.05.2005
• 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
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2005.01.006

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.