Identification of the novel mutation m.5658T>C in the mitochondrial tRNA(Asn) gene in a patient with myopathy, bilateral ptosis and ophthalmoparesis.

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.

Administration of exogenous erythropoietin beta affects lipid peroxidation and serum paraoxonase-1 activity and concentration in predialysis patients with chronic renal disease and anaemia.

1. Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase-1 (PON1) activity and an increased degree of oxidative stress compared with normal subjects. The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin (EPO) beta and iron on levels of antibodies against oxidized low-density lipoproteins (ox-LDL), as well as on serum PON1 activity and concentration, in predialysis patients with chronic renal disease. 2. Forty-nine patients with chronic renal failure and haemoglobin (Hb) < 11 g/dL were treated over a period of 6 months with EPObeta (80-120 U/kg per week, s.c.) and variable doses of iron. Selected biochemical variables were determined before and after treatment. 3. Treatment with EPObeta and iron was associated with a significant increase in mean (+/-SD) blood Hb concentration compared with pretreatment values (12.8 +/- 1.5 vs 9.9 +/- 0.6 g/dL, respectively; P < 0.001). The average dose of EPObeta was 6160 +/- 3000 U/week. After 6 months of treatment, compared with pretreatment values, the median levels (95% confidence intervals) of antibodies against ox-LDL were decreased (17.5 (10.6-24.4) vs 24.8 (11.5-38.1) U/mL, respectively; P < 0.001), serum PON1 activity was slightly but significantly increased (123.6 (76.1-343.6) vs 101.0 (50.0-332.5) U/L, respectively; P = 0.016) and the concentration of PON1 was significantly decreased (37.3 (11.8-76.2) vs 46.7 (24.6-98.0) mg/L, respectively; P < 0.001). There were no significant changes in total cholesterol, triglycerides or cholesterol fraction concentrations before and after treatment. 4. We suggest that EPObeta and iron treatment of anaemia promotes significant changes in serum PON1 activity and concentration and has a beneficial effect on oxidative stress in predialysis patients with chronic renal disease.