Mutation m.15923A>G in the MT-TT gene causes mild myopathy – case report of an adult-onset phenotype

Abstract Background: Only five patients have previously been reported to harbor mutations in the MT-TT gene encoding mitochondrial tRNA threonine. The m.15923A > G mutation has been found in three severely affected children. One of these patients died within days after birth and two had a phenotype of myoclonic epilepsy with ragged red fibers (MERRF) in early childhood. We have now found the mutation in an adult patient with mild myopathy. Case presentation: The patient is a 64-year-old Finnish man, who developed bilateral ptosis, diplopia and exercise intolerance in his fifties. Family history was unremarkable. Muscle histology showed cytochrome c-oxidase (COX) negative and ragged red fibres. The m.15923A > G mutation heteroplasmy was 33% in the skeletal muscle and 2% in buccal epithelial cells. The mutation was undetectable in the blood. Single-fibre analysis was performed and COX-negative fibres had a substantially higher heteroplasmy of 92%, than the normal fibres in which it was 43%. Conclusions: We report the fourth patient with m. 15923A > G and with a remarkably milder phenotype than the previous three patients. Our findings and recent biochemical studies suggest that the mutation m.15923A > G is a definite disease-causing mutation. Our results also suggest that heteroplasmy of the m.15923A > G mutation correlates with the severity of the phenotype. This study expands the catalog of the phenotypes caused by mutations in mtDNA

Effects of xylitol on xylitol-sensitive versus xylitol-resistant streptococcus mutans strains in a three-species in vitro biofilm

We studied the effects of xylitol on biofilms containing xylitol-resistant (Xr) and xylitol-sensitive (Xs) Streptococcus mutans, Actinomyces naeslundii and S. sanguinis. The biofilms were grown for 8 and 24 h on hydroxyapatite discs. The viable microorganisms were determined by plate culturing techniques and fluorescence in situ hybridization (FISH) was performed using a S. mutans-specific probe. Extracellular cell-bound polysaccharides (EPS) were determined by spectrofluorometry from single-species S. mutans biofilms. In the presence of 5 % xylitol, the counts of the Xs S. mutans decreased tenfold in the young (8 h) biofilm (p\0.05) but no effect was seen in the mature (24 h) biofilm. No decrease was observed for the Xr strains, and FISH confirmed these results. No differences were detected in the EPS production of the Xs S. mutans grown with or without xylitol, nor between Xr and Xs S. mutans strains. Thus, it seems that xylitol did not affect the EPS synthesis of the S. mutans strains. Since the Xr S. mutans strains, not inhibited by xylitol, showed no xylitol-induced decrease in the biofilms, we conclude that growth inhibition could be responsible for the decrease of the counts of the Xs S. mutans strains in the clinically relevant young biofilms. © 2012 Springer Science+Business Media, LLC.The work done at IPLA-CSIC (Spain) was funded by the project AGL2009-09445 (Spanish Ministry of Science and Innovation).Peer Reviewe

Case report:a novel frameshift mutation in the mitochondrial cytochrome c oxidase II gene causing mitochondrial disorder

Abstract Background: Mitochondrial cytochrome c oxidase 2, MT-CO2, encodes one of the three subunits, which form the catalytic core of cytochrome c oxidase (COX), complex IV. Mutations in MT-CO2 are rare and the associated phenotypes are variable including nonsyndromic and syndromic forms of mitochondrial diseases. Case presentation: We describe a 30-year-old man with cognitive decline, epilepsy, psychosis, exercise intolerance, sensorineural hearing impairment, retinitis pigmentosa, cataract and lactic acidosis. COX-deficient fibers and ragged red fibers were abundant in the muscle. Sequencing of mitochondrial DNA (mtDNA) revealed a novel frameshift mutation m.8156delG that was predicted to cause altered C-terminal amino acid sequence and to lead to truncation of the COX subunit 2. The deletion was heteroplasmic being present in 26% of the mtDNA in blood, 33% in buccal mucosa and 95% in muscle. Deletion heteroplasmy correlated with COX-deficiency in muscle histochemistry. The mother and the siblings of the proband did not harbor the deletion. Conclusions: The clinical features and muscle histology of the proband suggested a mitochondrial disorder. The m.8156delG deletion is a new addition to the short list of pathogenic mutations in the mtDNA-encoded subunits of COX. This case illustrates the importance of mtDNA sequence analysis in patients with an evident mitochondrial disorder

Thickness of peat influences the leaching of substances and greenhouse gas emissions from a cultivated organic soil

Abstract The off-site effects of agricultural organic soils include the leaching of N, P, and organic carbon (OC) to watercourses and CO₂, CH₄, and N₂O emissions into the atmosphere. The aim of this study was to quantify how the thickness of organic layers affects these loads. A 19.56-ha experimental field drained by subsurface pipes was established in Ruukki, northwestern Finland. Three plots had a 60–80 cm-thick sedge peat layer and three others had a thickness of 20 cm or less. The drainage pipes lie in mineral soil that, in this field, contains sulfidic material. This study documents the experimental settings and reports on the leaching of substances in the first two years, as well as CO₂, CH₄ and N₂O emissions during eight weeks in one summer. Total N (TN) and OC loads were higher from the thicker peat plots. The mean TN loads during a hydrological year were 15.4 and 9.2 kg ha⁻¹ from the thicker and thinner peat plots, respectively, with organic N representing 36% of TN load. Total P (TP) load averaged 0.27 kg ha⁻¹ yr⁻¹. Dissolved P load represented 63 and 36% of TP in the thicker peat area and only 23 and 13% in the thinner peat area, and was thus increased upon peat thickness. These N and P loads through the subsurface drainage system represented roughly 83% of TN and 64% of TP loads from this field. There were no clear differences in greenhouse gas emissions among the plots during the eight-week monitoring period. Slowly oxidizing sulfide in the subsoil resulted in annual leaching of 147 kg S ha⁻¹, almost ten times that of non-sulfidic soils. Our first results emphasize the effect of the peat thickness on the leaching of substances and warn about considering all organic soils as a single group in environmental assessments