TY - JOUR
T1 - Identification of the novel mutation m.5658T>C in the mitochondrial tRNA(Asn) gene in a patient with myopathy, bilateral ptosis and ophthalmoparesis
AU - Pinós, Tomàs
AU - Melià, Maria Jesús
AU - Ortiz, Nicolau
AU - Martinez-Vea, Albert
AU - Raventós-Estellé, Antoni
AU - Gallardo, Eduard
AU - Hernández-Losa, Javier
AU - Cámara, Yolanda
AU - Andreu, Antoni L.
AU - García-Arumí, Elena
PY - 2013/4/1
Y1 - 2013/4/1
N2 - We report a heteroplasmic novel mutation m.5658T>C in the mt-tRNAAsn 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. © 2013 Elsevier B.V.
AB - We report a heteroplasmic novel mutation m.5658T>C in the mt-tRNAAsn 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. © 2013 Elsevier B.V.
KW - Laser capture microdissection
KW - Mitochondria
KW - Mt-tRNA (Asn)
KW - Myopathy
U2 - 10.1016/j.nmd.2013.01.001
DO - 10.1016/j.nmd.2013.01.001
M3 - Article
SN - 0960-8966
VL - 23
SP - 330
EP - 336
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 4
ER -