| 1. |
- Arkblad, Eva L, et al.
(författare)
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Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy
- 2006
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Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 16:12, s. 830-8
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Tidskriftsartikel (refereegranskat)abstract
- Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by decreased levels of survival motor neuron protein (SMN). In the majority of cases, this decrease is due to absence of the SMN1 gene. Multiplex ligation-dependent probe amplification (MLPA) is a modern quantitative molecular method. Applied in SMA cases, it improves diagnostics by simultaneously identifying the number of copies of several target sequences in the SMN1 gene and in nearby genes. Using MLPA in clinical diagnostics, we have identified a previously unreported, partial deletion of SMN1 (exons 1-6) in two apparently unrelated Swedish families. This mutation would not have been detected by conventional diagnostic methods. This paper illustrates the broad clinical and genetic spectrum of SMA and includes reports of MLPA results and clinical descriptions of a patient with homozygous absence of SMN1 and only one SMN2 (prenatal onset SMA type 1), an asymptomatic woman with five SMN2 (lacking SMN1) and representative patients with SMA types 1, 2 and 3.
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| 2. |
- Eriksson, Annika K., et al.
(författare)
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Influence of iron addition on the oxygen-deficient Sr0.85Bi0.15Co1-xFexO3-delta (0.0 <= x <= 1.0) perovskites
- 2008
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Ingår i: Journal of Solid State Chemistry. - : Elsevier BV. - 0022-4596 .- 1095-726X. ; 181:8, s. 2031-2040
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Tidskriftsartikel (refereegranskat)abstract
- A series of oxygen-deficient Sr0.85Bi0.15Co1-xFexO3-delta (0.0 <= x <= 1.0) perovskite phases were prepared using solid-state reaction. Results of neutron powder diffraction analyses show that the introduction of Fe onto the B-site severely effects the long range coherence of the oxygen vacancy ordered, 14/mmm supercell, observed for the x = 0.0 sample. For x = 0.1 a smaller, a = b approximate to a(p), c approximate to 2a(p), P4/mmm supercell gives the best agreement to the diffraction data, whilst phases in the range 0.2 <= x <= 0.6 adopt disordered cubic perovskite structures. Pseudo-cubic, a = b approximate to a(p), c approximate to a(p), structures are found for x >= 0.8. Evidence of weak superstructures, reflecting local oxygen ordering, is also obtained from electron diffraction. For all oxygen-annealed phases the average structure reverts to cubic Pm (3) over barm. The as-prepared samples show G-type antiferromagnetic order at room temperature. The oxygen annealed x = 0.10, 0.25 and 1.0 samples display low-temperature spin-glass transitions.
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| 3. |
- Hammarén, Elisabet, et al.
(författare)
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Quantification of mobility impairment and self-assessment of stiffness in patients with myotonia congenita by the physiotherapist.
- 2005
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Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966. ; 15:9-10, s. 610-7
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Tidskriftsartikel (refereegranskat)abstract
- We investigated test-retest reliability and responsiveness in two functional measuring instruments, Timed Up&Go (TUG) and Timed-Stands Test (TST), and in three self-assessment scales, Visual Analogue Scale (VAS), Borg's Category-Ratio Scale (BorgCR10) and Myotonia Behaviour Scale (MBS) when quantifying myotonic stiffness and mobility impairment. These methods were used in the assessment of treatment efficacy of mexiletine. Six male patients with myotonia congenita followed a standardised protocol with time scoring and rest on two occasions, with and without mexiletine. Time scoring of TUG and TST and self-assessments of stiffness were performed. A 14-day stiffness diary was used at home. Timed Up&Go and TST showed very good test-retest agreement (ICC=0.87-0.95) and significant to change (P=0.005 and 0.001, respectively). All self-assessment scales revealed excellent responsiveness and good test-retest reliability. The measurement instruments possess great capacity to detect functional impairment in the myotonia congenita patient group, and sensibility to identify true changes due to treatment. When considering the results, three instruments are favoured; Timed Up&Go and BorgCR10 for short, and MBS for long-term evaluations.
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| 4. |
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| 5. |
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| 6. |
- Kollberg, Gittan, 1963, et al.
(författare)
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Low frequency of mtDNA point mutations in patients with PEO associated with POLG1 mutations.
- 2005
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 13:4, s. 463-9
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial myopathy in progressive external ophthalmoplegia (PEO) has been associated with POLG1 mutations. POLG1 encodes the catalytic alpha subunit of polymerase gamma and is the only polymerase known to be involved in mtDNA replication. It has two functionally different domains, one polymerase domain and one exonuclease domain with proofreading activity. In this study we have investigated whether mtDNA point mutations are involved, directly or indirectly, in the pathogenesis of PEO. Muscle biopsy specimens from patients with POLG1 mutations, affecting either the exonuclease or the polymerase domain, were investigated. Single cytochrome c oxidase (COX)-deficient muscle fibers were dissected and screened for clonally expanded mtDNA point mutations using a sensitive denaturing gradient gel electrophoresis analysis, in which three different regions of mtDNA, including five different tRNA genes, were investigated. To screen for randomly distributed mtDNA point mutations in muscle, two regions of mtDNA including deletion breakpoints were investigated by high-fidelity PCR, followed by cloning and sequencing. Long-range PCR revealed multiple mtDNA deletions in all the patients but not the controls. No point mutations were identified in single COX-deficient muscle fibers. Cloning and sequencing of muscle homogenate identified randomly distributed point mutations at very low frequency in patients and controls (<1:50 000). We conclude that mtDNA point mutations do not appear to be directly or indirectly involved in the pathogenesis of mitochondrial disease in patients with different POLG1 mutations.
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| 7. |
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| 8. |
- Kollberg, Gittan, 1963, et al.
(författare)
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Mitochondrial myopathy and rhabdomyolysis associated with a novel nonsense mutation in the gene encoding cytochrome c oxidase subunit I.
- 2005
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Ingår i: Journal of neuropathology and experimental neurology. - 0022-3069. ; 64:2, s. 123-8
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial DNA (mtDNA) mutations associated with rhabdomyolysis are rare but have been described in sporadic cases with mutations in the cytochrome b and cytochrome c oxidase (COX) genes and in 3 cases with tRNALeu mutation. We report a novel heteroplasmic G6708A nonsense mutation in the mtDNA COI gene encoding COX subunit I in a 30-year-old woman with muscle weakness, pain, fatigue, and one episode of rhabdomyolysis. Histochemical examination of muscle biopsy specimens revealed reduced COX activity in the majority of the muscle fibers (approximately 90%) and frequent ragged red fibers. Biochemical analysis showed a marked and isolated COX deficiency. Analysis of DNA extracted from single fibers revealed higher levels of the mutation in COX-deficient fibers (> 95%) compared with COX-positive fibers (1%-80%). The mutation was not detected in a skin biopsy, cultured myoblasts, or blood leukocytes. Nor was it identified in blood leukocytes from the asymptomatic mother, indicating a de novo mutation that arose after germ layer differentiation. Western blot analysis and immunohistochemical staining revealed that reduced levels of COX subunit I were accompanied by reduced levels of other mtDNA encoded subunits, as well as nuclear DNA encoded subunit IV, supporting the concept that COX subunit I is essential for the assembly of complex IV in the respiratory chain.
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| 9. |
- Lindberg, Christopher, et al.
(författare)
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MELAS syndrome in a patient with a point mutation in MTTS1.
- 2008
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 117:2, s. 128-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND, OBJECTIVE AND METHODS: We describe a female patient with a mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome. As a child, she developed epilepsy and stroke-like episodes giving cognitive impairment and ataxia but no hearing impairment. At the age of 44 years, she suffered a cerebral sinus thrombosis which was warfarin treated. One month later, she developed an episode of severe acidosis associated with encephalopathy and myelopathy. RESULTS: She was found to harbour a 7512T>C mutation in the mitochondrial encoded tRNA(Ser(UCN)) gene (MTTS1). The mutation load was 91% in muscle and 24% in blood. Enzyme histochemical analysis of the muscle tissue showed numerous cytochrome c oxidase (COX)-negative fibres. Restriction fragment length polymorphism (RFLP) analysis of single muscle fibres showed significantly higher level (median 97%, range: 94-99%) of the mutation in the COX-negative fibres compared with COX-positive fibres (median 36%, range: 12-91%), demonstrating the pathogenic effect of the mutation. Different levels of heteroplasmy (range 34-61%) were detected in hair shafts analysed by RFLP. CONCLUSION: This case adds to the spectrum of clinical presentations, i.e. sinus thrombosis, in patients having MTTS1 mutations.
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| 10. |
- Lindberg, Christopher, et al.
(författare)
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Raised troponin T in inclusion body myositis is common and serum levels are persistent over time
- 2006
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Ingår i: Neuromuscul Disord. - : Elsevier BV. ; 16:8, s. 495-7
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac Troponin T (cTnT), creatine kinase (CK) and creatine kinase isoenzyme MB (CKMB) were measured in 42 consecutive patients with sporadic inclusion body myositis (s-IBM). 26 patients (62%) had a cTnT level >0.05mug/L, the cut off used in the diagnosis of myocardial infarction. The cTnT levels correlated somewhat more closely to CKMB (rho=0.83, p<0.0001) than to CK (rho=0.60, p<0.0001). Patients on immunosuppressive treatment had lower cTnT levels than untreated, while there were no significant differences according to age, disease duration or gender. Repeated samples in 26 patients showed that the cTnT levels were essentially unchanged over time up to 17 months. None of the patients had signs of myocardial damage or renal failure at time of sampling. It may be of value to analyse cTnT at some occasion(s) in s-IBM patients.
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