Identification of the novel mutation m.5658T > C in the mitochondrial tRNA(Asn) gene in a patient with myopathy, bilateral ptosis and ophthalmoparesis
Por:
Pinos, T, Melia, MJ, Ortiz, N, Martinez-Vea, A, Raventos-Estelle, A, Gallardo, E, Hernandez-Losa, J, Camara, Y, Andreu, AL, Garcia-Arumi, E
Publicada:
1 abr 2013
Resumen:
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. (c) 2013 Elsevier B.V. All rights reserved.
Filiaciones:
Pinos, T:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron Inst Recerca VHIR, Dept Patol Mitocondrial & Neuromuscular, E-08193 Barcelona, Spain
ISCIII, CIBERER, Barcelona, Spain
Melia, MJ:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron Inst Recerca VHIR, Dept Patol Mitocondrial & Neuromuscular, E-08193 Barcelona, Spain
ISCIII, CIBERER, Barcelona, Spain
Ortiz, N:
Hosp Univ St Joan, Seccio Neurol, Reus, Spain
Martinez-Vea, A:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan 23, Serv Nephrol, Tarragona, Spain
Raventos-Estelle, A:
Univ Rovira & Virgili, Hosp Univ Tarragona Joan 23, Pathol Serv, Tarragona, Spain
Gallardo, E:
Univ Autonoma Barcelona, Inst Recerca Hosp Santa Creu & St Pau, Lab Malalties Neuromusculars, E-08193 Barcelona, Spain
Hernandez-Losa, J:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron Inst Recerca VHIR, Serv Anat Patol, E-08193 Barcelona, Spain
Camara, Y:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron Inst Recerca VHIR, Dept Patol Mitocondrial & Neuromuscular, E-08193 Barcelona, Spain
ISCIII, CIBERER, Barcelona, Spain
Andreu, AL:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron Inst Recerca VHIR, Dept Patol Mitocondrial & Neuromuscular, E-08193 Barcelona, Spain
ISCIII, CIBERER, Barcelona, Spain
Garcia-Arumi, E:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron Inst Recerca VHIR, Dept Patol Mitocondrial & Neuromuscular, E-08193 Barcelona, Spain
ISCIII, CIBERER, Barcelona, Spain
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