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jtitle_s:("Acta mol")
1.  Intravenous immunoglobulin therapy in two patients with myasthenia gravis and pemphigus vulgaris 
Acta Myologica  2009;28(3):101-102.
Various forms of pemphigus have been reported to occur with myasthenia gravis (MG), with and without thymoma. We described two cases of pemphigus vulgaris associated with MG without thymoma.
Case 1. A 44 year-old woman presented with 3 years history of pemphigus vulgaris. Three years later, she developed myasthenic symptoms with elevated level of anti-acetylcholine receptor (AChR) antibodies - 5.2 nmol/L. She was thymectomised and we revealed only hyperplastic thymus.
Case 2. A 64-year-old woman had a general fatigue and intermittent double vision. She was diagnosed as MG three years later. Two months before she diagnosed as MG, she had pruritic erythematous, erosive and bullous lesions on her body and extremities.
Oral prednisolon, pyridostigmine bromide and azathioprine or cyclophosphamide didn`t adequately control MG and pemphigus in our patients, so they received intravenous immunoglobulins of 0.4 g/kg for 5 consecutive days. After that therapy, our patients markedly improved.
Conclusion: The precise pathological mechanisms of the association between pemphigus and MG are not fully understood. The thymus has been suggested to be a possible common origin of autoimmune response in these disorders.
PMCID: PMC2858944  PMID: 20476669
Myasthenia gravis; pemphigus vulgaris; intravenous immunoglobulins
2.  Severe phenotype of a patient with autosomal recessive centronuclear myopathy due to a BIN1 mutation 
Acta Myologica  2009;28(3):91-93.
Centronuclear myopathy (CNM) is a rare hereditary congenital myopathy characterized by muscular hypotonia and abnormal centralization of nuclei in muscle fibers. The autosomal recessive (AR) form presents from birth to childhood, followed by a mild progression of muscle weakness. Despite recently identified genetic loci in the AR form, genotype-phenotype correlations are poorly established. Our index case is a 17 year old boy with recessive CNM causing loss of ambulation at 13 years of age and requiring ventilatory assistance nightly. Recent genetic testing revealed a c.1723A > T mutation in the BIN1 gene. The phenotype of the index case contrasts to previously published cases, where recessive CNM patients have lost ambulation in their 20s and have not required ventilatory assistance. The disease severity of our index case, carrying a c.1723A > T mutation, widens the phenotypic spectrum of AR CNM to include earlier loss of ambulation and respiratory failure.
PMCID: PMC2858945  PMID: 20476667
Centronuclear myopathy; BIN1; phenotype
3.  Markers of degeneration and regeneration in Duchenne muscular dystrophy 
Acta Myologica  2009;28(3):94-100.
Dystrophin deficiency associated with Duchenne muscular dystrophy (DMD) results in chronic inflammation and severe skeletal muscle degeneration, where the extent of muscle fibrosis contributes to disease severity. The microenvironment of dystrophic muscles is associated with variation in levels of markers of degeneration and regeneration. Since in dystrophic muscle apoptosis precedes necrosis, markers of apoptosis can be used as indicators of degeneration, while regeneration can be measured in terms of cytokines and growth factor expression”; and then throughout the text use “markers of apoptosis/degeneration. The present study is an attempt to evaluate the extent of degeneration and regeneration in DMD patient blood. Subjects were 24 boys with DMD diagnosed at the molecular level versus 20 age and socioeconomic matching healthy boys. In their blood, levels of Fas and FasL and Bax/Bcl-2 and plasma DNA fragmentation were measured as markers of apoptosis. The cytokine tumor necrosis factor alfa (TNF-α), and the growth factors: basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were measured as markers of regeneration. Plasma DNA fragmentation (0.38% ± 0.12 vs. 0.2% ± . 0.1.5) and Fas (9.9 ± 2.8 vs. 2 ± 0.1, p < 0.001) together with FasL mRNA expression in circulating lymphocytes (0.47 ± .09 vs. 0.24 ± .04, p < 0.001) were significantly increased in DMD patients compared to controls. There was a significant increase in Bax (0.19 ± 0.7 vs. 0.05 ± 0.1, p < 0.00001) expression and a significant decrease in Bcl-2 protein (6.4 ± 1.6 vs10 ± 2.8, p < 0.00001) as compared to controls. Among markers of regeneration, TNF- α (30.2 ± 9.5 vs. 3.6 ± 0.9) and bFGF (21.7 ± 10.3 vs. 4.75 ± 2.2) were significant increased while VEGF was significantly decreased (190 ± 115 vs. 210 ± 142.) in blood of DMD patients compared to controls. Our results indicate that Fas/FasL and Bax/Bcl-2 are involved in muscle atrophy and degeneration in DMD patients, while regeneration process does not cope with the degeneration.
PMCID: PMC2858946  PMID: 20476668
Apoptosis; basic fibroblast growth factor; Duchenne muscular dystrophy
6.  Unusual association of FSHD and extramedullary thoracic tumour in the same patient: a case report 
Acta Myologica  2009;28(2):76-79.
In the recent literature the association of facioscapulohumeraldystrophy (FSHD) with some hereditary neuromuscular diseases in the same patient has been reported. We present the first case in which the genetically confirmed familial FSHD is associated with an extramedullary thoracic tumour.
PMCID: PMC2858950  PMID: 20128141
Facioscapulohumeral dystrophy; atypical phenotype; extramedullary tumour
7.  The progress reports on the development of therapies of Duchenne muscular dystrophy 
Acta Myologica  2009;28(2):62-65.
The roots of the progress reports on the development of therapies for Duchenne muscular dystrophy (DMD) that since 2000 have been produced at Breitnau/Germany and distributed to the parents of DMD patients cover over 30 years of continual occupation with this disease. The beginning was marked by the development of an early detection programme for the genetic disposition for DMD in infant boys. The next step was the organisation of workshops on the management of DMD and the writing of progress reports on these and other relevant conferences. Getting acquainted with the ideas of the protagonists in the research field by holding interviews was a decisive prerequisite for this activity. This took place in tandem with the development of a new kind of multiplex “family letters” that attempted to answer frequently asked questions to many DMD families at the same time.
When – with the beginning of the new millennium – the endeavours towards gene therapies for DMD started to boom all over the scientific world, progress reports designed to keep the families informed about research on DMD treatment were added to the family letters. These reports that give an account of the latest state of the research are written in a plain language that can be understood by laypersons. In the meantime the reports have adopted the character of reviews that are updated annually. They are written in English and German and translated into Spanish and many other languages.
PMCID: PMC2858951  PMID: 20128138
Duchenne muscular dystrophy; CK screening; multiplex family letters; progress reports; gene therapy; exon skipping
8.  Mild form of Charcot-Marie-Tooth type 1X disease caused by a novel Cys179Gly mutation in the GJB1/Cx32 gene 
Acta Myologica  2009;28(2):72-75.
Charcot-Marie-Tooth type 1X (CMT1X) disease is inherited as an X-linked dominant trait. Female CMT1X patients are usually mildly affected or even asymptomatic carriers of mutations in the GJB1 gene coding for a gap junction protein called connexin-32 (Cx32).
In this report, a five-generation CMT1X family is described from which the new mutation in the GJB1 gene Cys179Gly was identified.
The Cys179Gly mutation is located in the highly conservative domain of the Cx32 protein. Previous functional studies performed in the oocyte system have shown that point mutations in the highly conserved Cx32 cysteine residues result in a complete loss of function of the gap junction. However, despite severe biochemical defects, the Cys179Gly mutation segregates with a mild CMT1X phenotype.
This study further documents a discrepancy between biochemical effects of GJB1 mutations and the CMT1X phenotype.
PMCID: PMC2858952  PMID: 20128140
CMT1X disease; novel GJB1 gene mutation; Cx32 protein; loss of function mutations
9.  Sporadic inclusion body myositis: variability in prevalence and phenotype and influence of the MHC 
Acta Myologica  2009;28(2):66-71.
Sporadic inclusion body myositis (sIBM) is the most common myopathy presenting over the age of 40 years but its prevalence varies considerably in different populations. Genetic factors play a part in the pathogenesis of sIBM and in Caucasians susceptibility has been linked to the HLA-DR3 allele and the 8.1 MHC ancestral haplotype (AH) which is also associated with other autoimmune diseases. The variable prevalence of sIBM in different populations may be related to differences in the population frequency of this haplotype. Our recent observations indicate that the clinical phenotype at presentation is also quite variable and that the influence of the MHC is more complex than previously appreciated with HLA alleles also having modifying effects on the age-at-onset, severity and rate of progression of the disease. Recent recombinant mapping studies of polymorphisms in the Class II/III regions of the MHC by our group have further refined the susceptibility region and have identified a number of candidate genes warranting further investigation. The significance of these findings for the pathogenesis of the disease is discussed.
PMCID: PMC2858953  PMID: 20128139
S-IBM; prevalence; phenotype; MHC alleles
11.  Editorial 
Acta Myologica  2009;28(1):1.
PMCID: PMC2859627
12.  Encephalomyopathies caused by abnormal nuclear-mitochondrial intergenomic cross-talk 
Acta Myologica  2009;28(1):2-11.
Autosomal dominant Progressive External Ophthalmoplegias are Mendelian disorders characterized by the accumulation of multiple deletions of mitochondrial DNA in critical tissues. Most of the Autosomal dominant Progressive External Ophthalmoplegias families carry heterozygous mutations in one of three genes: ANT1, encoding the muscle-heart specific mitochondrial adenine nucleotide translocator, Twinkle, encoding the mitochondrial DNA helicase, and POLG1, encoding the catalytic subunit of the mitochondrial DNA-specific polymerase. Mutations in both POLG1 alleles are also found in autosomal recessive Progressive External Ophthalmoplegias sibships with multiple affected members and in apparently sporadic cases. In addition, recessive POLG1 mutations are responsible for three additional diseases: Alpers-Huttenlocher hepatopathic poliodystrophy, Sensory-Ataxic Neuropathy Dysarthria and Ophthalmoplegia and juvenile SpinoCerebellar Ataxia-Epilepsy syndrome. Mitochondrial neuro-gastro-intestinal encephalomyopathy is an autosomal recessive disorder of juvenile onset, caused by mutations in the gene encoding Thymidine Phosphorylase. Thymidine Phosphorylase is involved in the control and maintenance of the pyrimidine nucleoside pool of the cell. Finally, mitochondrial DNA depletion syndrome is a heterogeneous group of disorders characterized by a reduction in mitochondrial DNA copy number. Clinically, they include a myopathic form, a more generalized encephalomyopathic form and a fatal infantile hepato-cerebral syndrome leading to rapidly progressive liver and brain failure. To date, eight genes have been associated with mitochondrial DNA depletion syndrome. Novel disease genes have recently been added to this list, including OPA1 and GFER, and new clinical variants add further complexity to this expanding area of mitochondrial medicine.
PMCID: PMC2859628  PMID: 19772189
Mitochondrial DNA; oxidative phosphorylation; mitochondrial disorders; MtDNA multiple deletions; MtDNA depletion
14.  Mitochondrial disorders of the nuclear genome 
Acta Myologica  2009;28(1):16-23.
Mitochondrial myopathies are regulated by two genomes: the nuclear DNA, and the mitochondrial DNA. While, so far, most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial DNA, a new field of investigation is that of syndromes due to mutations in the nuclear DNA. These latter disorders have mendelian inheritance.
Three representative cases have been selected: one with COX deficiency and a Leigh syndrome due to a SURF1 gene mutation, one due to a defect of Coenzyme Q synthesis and one with dominant optic atrophy due to a mutation in the OPA1 gene.
Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission.
PMCID: PMC2859630  PMID: 19772191
SURF1; ataxia; optic atrophy
15.  High frequency of Friedreich’s ataxia carriers in the Paphos district of Cyprus 
Acta Myologica  2009;28(1):24-26.
A cluster of Friedreich’s ataxia patients has been previously investigated in two neighbouring villages of the Paphos district of Cyprus. Molecular genetic studies revealed that all patients had the most common mutation, a homozygous expansion of the GAA triplet repeat in the first intron of the frataxin gene. The present study is aimed at estimating the mutation carrier frequency in the broader area of Paphos. Overall, 1050 individuals originating from the Paphos district took part in the programme. Blood samples were collected for a period of 18 months, on a voluntary basis, after signing a consent form, and analysis of the GAA triplet repeat was performed. The frequency of mutation carriers in the broader area of the Paphos district, and excluding the two neighbouring cluster villages, is estimated to be high. We recommend that an organized prevention programme be implemented to cover the population from this region.
PMCID: PMC2859631  PMID: 19772192
Friedreich’s ataxia; GAA repeat expansion; population screening; high carrier frequency
16.  Welcoming Address 
Acta Myologica  2009;28(1):28.
PMCID: PMC2859632

Results 1-25 (49)