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- 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
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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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- Ohlsson, M., et al.
(författare)
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Follow-up of nemaline myopathy in two patients with novel mutations in the skeletal muscle alpha-actin gene (ACTA1)
- 2004
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Ingår i: Neuromuscular Disorders. - : Institute of Information Science. - 0960-8966 .- 1873-2364. ; 14:8-9, s. 471-475
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Tidskriftsartikel (refereegranskat)abstract
- Nemaline myopathy has been associated with mutations in five different genes, which all encode protein components of the sarcomeric thin filaments. We report follow-up studies in two children with mutations not previously described in skeletal muscle alpha-actin (ACTA1). Case 1 was a male patient who after birth suffered from pronounced muscle weakness and hypotonia. Muscle biopsy showed small fibers with numerous rods. He failed to achieve any motor milestones. At the age of 17 he required 24 h ventilator support. He could not lift his arms against gravity, but he could use his hands to control his electric wheelchair. The muscle biopsy showed marked replacement of muscle tissue by fat and connective tissue. Only few fibers showed nemaline rods. He had a de novo, heterozygous mutation, G268D in ACTA1. Case 2 was a female patient with feeding difficulties and mild hypotonia in the neonatal period. Muscle biopsy showed hypoplastic muscle fibers and numerous rods. At 11 years of age she walked and moved unhindered and could run fairly well. She had a de novo, heterozygous mutation, K373E, in ACTA1. These two patients illustrate the marked variability in the clinical features of nemaline myopathy in spite of similar muscle pathology in early childhood. The severe muscle atrophy with replacement of fat and connective tissue in case 1 demonstrates the progressive nature of nemaline myopathy in some cases. The described two mutations add to the previously reported mutations in ACTA1 associated with nemaline myopathy.
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