| 11. |
- Chakrapani, A, et al.
(författare)
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Disorder of tyrosine metabolism
- 2006
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Ingår i: Inborn metabolic diseases. Diagnosis and treatment.. - Heidelberg : Springer Medizin Verlag Heidelberg. - 9783540287834 ; , s. 233-242
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 12. |
- Darin, Niklas, 1964, et al.
(författare)
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3-methylcrotonyl-CoA carboxylase deficiency and severe multiple sclerosis.
- 2007
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Ingår i: Pediatric neurology. - : Elsevier BV. - 0887-8994. ; 36:2, s. 132-4
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Tidskriftsartikel (refereegranskat)abstract
- This report describes a female with isolated 3-methylcrotonyl-CoA carboxylase deficiency. She had a mild Reye-like episode, loss of scalp hair, psychomotor retardation, and an attention-deficit hyperactivity disorder. The diagnosis was made at 13 years of age when she developed relapsing remitting multiple sclerosis with a malignant course. Treatment with steroids had initially a good therapeutic effect on the relapses. The response to interferon beta-1a treatment was poor. On mitoxantrone treatment there was a considerable neurologic recovery.
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| 13. |
- Darin, Niklas, 1964, et al.
(författare)
-
Mitochondrial myopathy with exercise intolerance and retinal dystrophy in a sporadic patient with a G583A mutation in the mt tRNA(phe) gene
- 2006
-
Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 16:8, s. 504-6
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Tidskriftsartikel (refereegranskat)abstract
- We describe a second patient with the 583G>A mutation in the tRNA(phe) gene of mitochondrial DNA (mtDNA). This 17-year-old girl had a mitochondrial myopathy with exercise intolerance and an asymptomatic retinopathy. Muscle investigations showed occasional ragged red fibers, 30% cytochrome c oxidase (COX)-negative fibers, and reduced activities of complex I+IV in the respiratory chain. The mutation was heteroplasmic (79%) in muscle but undetectable in other tissues. Analysis of single muscle fibers revealed a significantly higher level of mutated mtDNA in COX-negative fibers. Our study indicates that the 583G>A mutation is pathogenic and expands the clinical spectrum of this mutation.
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| 14. |
- Holme, Elisabeth, 1947
(författare)
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Disorders of tyrosine degradation
- 2006
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Ingår i: Physician´s guide to the treatment and follow-up of metabolic diseases. - berlin, Heidelberg, New York : Springer Verlag. - 9783540229544 ; , s. 49-56
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Holme, Elisabeth, 1947, et al.
(författare)
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Tyrosine Metabolism
- 2014
-
Ingår i: In N.Blau et al. (eds.) Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. - Berlin Heidelberg : Springer-Verlag. - 9783642403378 ; , s. 23-31
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 16. |
- Horvath, Rita, et al.
(författare)
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Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.
- 2009
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 132:Pt 11, s. 3165-74
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Tidskriftsartikel (refereegranskat)abstract
- Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.
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| 17. |
- Houshmand, Massoud, et al.
(författare)
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Different tissue distribution of a mitochondrial DNA duplication and the corresponding deletion in a patient with a mild mitochondrial encephalomyopathy: deletion in muscle, duplication in blood.
- 2004
-
Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966. ; 14:3, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale heteroplasmic mtDNA rearrangements were identified in a 57-year-old woman with chronic depressive disorder, hearing-loss, diabetes mellitus and a slowly progressive encephalomyopathy. A high percentage of a 24.2 kb duplicated molecule was found in lymphocytes whereas the corresponding deletion dimer dominated in muscle. PCR and Southern blot analyses were used to identify a 7658 bp duplication/deletion fragment. The duplicated mtDNA disrupted the cytochrome oxidase subunit I and cytochrome b genes at a position where there were no direct repeats. Duplicated mtDNA was not observed in the mother and brother of the patient. Histochemical analysis of skeletal muscle demonstrated pathological accumulation of mitochondria in cytochrome c oxidase negative fibers. In situ hybridization demonstrated only deleted mtDNA in cytochrome c oxidase negative fibres. We conclude that occurrence of deleted mtDNA correlates with phenotypic expression and that the duplicated mtDNA might serve as a generator of deletions, but is not directly pathogenic.
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| 18. |
- Kollberg, Gittan, 1963, et al.
(författare)
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A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.
- 2009
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Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 0960-8966. ; 19:2, s. 147-50
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Tidskriftsartikel (refereegranskat)abstract
- This report describes two brothers, both deceased in infancy, with severe depletion of mitochondrial DNA (mtDNA) in muscle tissue. Both had feeding difficulties, failure to thrive, severe muscular hypotonia and lactic acidosis. One of the boys developed a renal proximal tubulopathy. A novel homozygous c.686 G-->T missense mutation in the RRM2B gene, encoding the p53-inducible ribonucleotide reductase subunit (p53R2), was identified. This is the third report on mutations in RRM2B associated with severe mtDNA depletion, which further highlights the importance of de novo synthesis of deoxyribonucleotides (dNTPs) for mtDNA maintenance.
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| 19. |
- Kollberg, Gittan, 1963, et al.
(författare)
-
Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency myopathy.
- 2009
-
Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 1873-2364 .- 0960-8966. ; 19:12, s. 833-6
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Tidskriftsartikel (refereegranskat)abstract
- Iron-sulphur cluster deficiency myopathy is caused by a deep intronic mutation in ISCU resulting in inclusion of a cryptic exon in the mature mRNA. ISCU encodes the iron-sulphur cluster assembly protein IscU. Iron-sulphur clusters are essential for most basic redox transformations including the respiratory-chain function. Most patients are homozygous for the mutation with a phenotype characterized by a non-progressive myopathy with childhood onset of early fatigue, dyspnoea and palpitation on trivial exercise. A more severe phenotype with early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy is caused by a missense mutation in compound with the intronic mutation. Treatment of cultured fibroblasts derived from three homozygous patients with an antisense phosphorodiamidate morpholino oligonucleotide for 48 h resulted in 100% restoration of the normal splicing pattern. The restoration was stable and after 21 days the correctly spliced mRNA still was the dominating RNA species.
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| 20. |
- Kollberg, Gittan, 1963, et al.
(författare)
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Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy
- 2009
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 132:8, s. 2170-2179
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Tidskriftsartikel (refereegranskat)abstract
- Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The disease has so far only been identified in northern Sweden. The clinical, histochemical and biochemical phenotype is very homogenous and the patients are homozygous for a deep intronic IVS5 382GC splicing affecting mutation in ISCU, which encodes the differently spliced cytosolic and mitochondrial ironsulphur cluster assembly protein IscU. Ironsulphur cluster containing proteins are essential for iron homeostasis and respiratory chain function, with IscU being among the most conserved proteins in evolution. We identified a shared homozygous segment of only 405 000 base pair with the deep intronic mutation in eight patients with a phenotype consistent with the original description of the disease. Two other patients, two brothers, had an identical biochemical and histochemical phenotype which is probably pathognomonic for muscle ironsulphur cluster deficiency, but they presented with a disease where the clinical phenotype was characterized by early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy. The brothers were compound heterozygous for the deep intronic mutation and had a c.149 GA missense mutation in exon 3 changing a completely conserved glycine residue to a glutamate. The missense mutation was inherited from their mother who was of Finnish descent. The intronic mutation affects mRNA splicing and results in inclusion of pseudoexons in most transcripts in muscle. The pseudoexon inclusion results in a change in the reading frame and appearance of a premature stop codon. In western blot analysis of protein extracts from fibroblasts, there was no pronounced reduction of IscU in any of the patients, but the analysis revealed that the species corresponding to mitochondrial IscU migrates slower than a species present only in whole cells. In protein extracted from isolated skeletal muscle mitochondria the western blot analysis revealed a severe deficiency of IscU in the homozygous patients and appearance of a faint new fraction that could represent a truncated protein. There was only a slight reduction of mitochondrial IscU in the compound heterozygotes, despite their severe phenotype, indicating that the IscU expressed in these patients is non-functional.
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