| 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. |
- Darin, Niklas, 1964, et al.
(författare)
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Mitochondrial myopathy with exercise intolerance and retinal dystrophy in a sporadic patient with a G583A mutation in the mt tRNA(phe) gene
- 2006
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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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| 3. |
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| 4. |
- 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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| 5. |
- Oldfors Hedberg, Carola, 1969, et al.
(författare)
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Early onset cardiomyopathy in females with Danon disease
- 2015
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966. ; 25:6, s. 493-501
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Tidskriftsartikel (refereegranskat)abstract
- Danon disease is caused by mutations in the lysosome-associated membrane protein-2 gene, LAMP2, located on the X chromosome. Female carriers with LAMP2 mutations most often present with late onset cardiomyopathy and slow disease progress; however, there are unusual cases that emerge early and show a more severe disease course. We investigated the explanted heart and skeletal muscle biopsies in two girls, aged ten and thirteen years, who underwent cardiac transplantation because of hypertrophic cardiomyopathy secondary to LAMP2 mutations and a 41-year old female with late-onset familial LAMP2 cardiomyopathy with more typical clinical phenotype. The two girls in contrast had clinical features that mimicked severe primary hypertrophic cardiomyopathy caused by mutations in genes encoding sarcomeric proteins. Immunohistochemistry in cardiac muscles showed a remarkable pattern with lack of LAMP2 protein in large regions including thousands of cardiomyocytes that also showed myocyte hypertrophy, lysosomial enlargement and disarray. In other equally large regions there were preserved LAMP2 expression and nearly normal histology. The skeletal muscle biopsy revealed no pathological changes. An uneven distribution of LAMP2 protein may cause deleterious effects depending on which regions of the myocardium are lacking LAMP2 protein in spite of an overall moderate reduction of LAMP2 protein. This may be a more common mechanism behind early aggressive disease in females than an overall skewed X-chromosome inactivation in the tissue. (C) 2015 Elsevier B.V. All rights reserved.
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| 6. |
- Oldfors Hedberg, Carola, 1969, et al.
(författare)
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Grand paternal inheritance of X-linked myotubular myopathy due to mosaicism, and identification of necklace fibers in an asymptomatic male.
- 2017
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Ingår i: Neuromuscular disorders : NMD. - : Elsevier BV. - 1873-2364 .- 0960-8966. ; 27:9, s. 843-847
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Tidskriftsartikel (refereegranskat)abstract
- X-linked recessive myotubular myopathy (XLMTM) is a disorder associated with mutations in the myotubularin gene (MTM1) that usually affects boys, with transmission of the mutated allele from the mother. Here we describe a family with unexpected grand paternal transmission of a novel mutation in MTM1 (c.646_648dupGTT; p.Val216dup) identified in a severely affected infant boy with a centronuclear myopathy. We confirmed the carrier status of the mother, but surprisingly we found that her father was a carrier of the mutated MTM1 gene together with wild-type MTM1. A muscle biopsy from the grandfather revealed occasional typical necklace fibers with internalized nucleus, which is typically found in MTM1-associated myopathies. Further analysis of the grandfather revealed equal amounts of DNA with the wild-type sequence and DNA with the c.646_648dupGTT variant in five different tissues examined. In the presence of a normal karyotype (46,XY) in the grandfather and no evidence of intragenic duplication of MTM1, the result was interpreted as postzygotic mosaicism and the mutation had probably occurred at the first mitosis of the zygote. This study demonstrates the importance of considering the possibility of paternal transmission in families with severe X-linked disorders. The muscle biopsy with the finding of typical necklace fibers was important to further establish the pathogenicity of the novel MTM1 mutation.
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| 7. |
- Söderpalm, Ann-Charlott, 1961, et al.
(författare)
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Low bone mineral density and decreased bone turnover in Duchenne muscular dystrophy
- 2007
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 17:11-12, s. 919-928
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Tidskriftsartikel (refereegranskat)abstract
- This cross-sectional study examined bone mineral density, bone turnover, body composition and calciotropic hormones in 24 boys with Duchenne muscular dystrophy (DMD) (2.3-19.7 years), most of whom were being treated with prednisolone, and 24 age-matched healthy boys. Our study demonstrated lower bone mineral density in the DMD group for total body, spine, hip, heel and forearm measurements. These differences between DMD patients and controls increased with increasing age. Biochemical markers of both bone formation and resorption revealed reduced bone turnover in DMD patients. The fracture rate was not higher in DMD patients. The DMD group had low vitamin D levels but high leptin levels in comparison with the control group. Muscle strength correlated with bone mineral density assessed at the hip and heel in the DMD group. Interventions that increase bone formation should be considered, as DMD patients have reduced bone turnover in addition to their low bone mineral density. © 2007 Elsevier B.V. All rights reserved.
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| 8. |
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| 9. |
- Tajsharghi, Homa, et al.
(författare)
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Early onset myopathy with a novel mutation in the Selenoprotein N gene (SEPN1)
- 2005
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Ingår i: Neuromuscular Disorders. - : Elsevier. - 0960-8966 .- 1873-2364. ; 15:4, s. 299-302
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in SEPN1 have been associated with three autosomal recessive congenital myopathies, including rigid spine muscular dystrophy, multiminicore disease and desmin-related myopathy with Mallory body-like inclusions. These disorders constitute the SEPN1 related myopathies (SEPN-RM). On the basis of clinical and laboratory features compatible with SEPN-RM, we performed mutation analysis of SEPN1 in 11 unrelated patients and found one case with pathogenic mutations. He showed early onset axial muscle weakness and developed scoliosis with respiratory insufficiency. Muscle biopsy showed increased variability of fiber size and slight, focal increase of connective tissue. A few fibers showed mini-core changes. SEPN1 mutation analysis revealed that the patient was a compound heterozygote: a previously described insertion (713-714 insA), and a novel nonsense mutation (R439stop).
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| 10. |
- Thorarinsdottir, Brynja Kristin, 1973, et al.
(författare)
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Muscular dystrophies and congenital myopathies in childhood
- 2011
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Ingår i: Neuromuscular Disorders. - 0960-8966. ; 21:9-10, s. 746-747
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Muscular dystrophies and congenital myopathies in childhood. Muscular dystrophies and congenital myopathies often produce a similar clinical picture of muscle weakness and atrophy. Population studies that include muscular dystrophies and congenital myopathies are rare, it is not well studied how common these disorders are. The aim of the study was to identify all the patients diagnosed with muscular dystrophies and congenital myopathies in childhood over a thirty year period, between 1979 and 2009. The geographic area studied was the region of western Sweden. We analyzed registers from local and regional pediatric hospitals and local and regional child rehabilitations, registers of muscle biopsies, neurophysiologic examinations and genetic analyses. The total number of identified cases were 221 patients. 131 patients with muscular dystrophies that were divided into 61 patients with Duchenne muscular dystrophy, 12 with Becker muscular dystrophy, 21 with limb-girdle muscular dystrophy, 15 with facioscapulohumeral muscle dystrophy, 3 with Emery-Dreifuss muscle dystrophy and 19 with congenital muscle dystrophy. 90 patients were diagnosed with congenital myopathy. The study will present the incidence, prevalence and relative frequency of these disorders in childhood.
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