title: Identification of the novel mutation m.5658T>C in the mitochondrial tRNA(Asn) gene in a patient with myopathy, bilateral ptosis and ophthalmoparesis.
abstract: We report a heteroplasmic novel mutation m.5658T>C in the mt-tRNA(Asn) gene in a patient who initially presented myopathy, bilateral ptosis and ophthalmoparesis and several years later developed a non-nephrotic proteinuria. The muscle biopsy showed cytochrome c oxidase (COX) negative and ragged red fibers and in the kidney biopsy that was taken in order to identify the causes of non-nephrotic proteinuria, a focal segmental glomerulosclerosis was observed. Using laser capture microdissection we isolated COX negative fibers and COX positive fibers from the muscle of the patient and determined that there was a clear increase in the mutation load in the COX negative muscle fibers. However, the low degree of mutation load found in the renal biopsy of the patient does not allow us to conclude that the m.5658T>C mutation is responsible for focal glomerulosclerosis. Additionally, we hypothesize that the mutated m.5658T nucleotide might be structurally relevant, as it is one of the fifteen nucleotides conserved in all the species analyzed and is situated contiguously to the discriminator base in the 3'end of the mt-tRNA, where the tRNase Z cleaves the 3' trailer sequence during mt-tRNA maturation.
authors: Departament de Patología Mitocondrial i Neuromuscular, Hospital Universitari Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Tomàs
authors: T
authors: Pinós
authors: Maria Jesús
authors: MJ
authors: Melià
authors: Nicolau
authors: N
authors: Ortiz
authors: Albert
authors: A
authors: Martinez-Vea
authors: Antoni
authors: A
authors: Raventós-Estellé
authors: Eduard
authors: E
authors: Gallardo
authors: Javier
authors: J
authors: Hernández-Losa
authors: Yolanda
authors: Y
authors: Cámara
authors: Antoni L
authors: AL
authors: Andreu
authors: Elena
authors: E
authors: García-Arumí
mesh_terms: D000328:Adult; D001763:Blepharoptosis / Q000150:complications / Q000235:genetics; D050259:Genes, Mitochondrial / Q000235:genetics*; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D017240:Mitochondrial Myopathies / Q000150:complications / Q000235:genetics*; D009154:Mutation; D009886:Ophthalmoplegia / Q000150:complications / Q000235:genetics*; D012348:RNA, Transfer, Asn / Q000235:genetics*
chemical_list: D012348:RNA, Transfer, Asn