Analysis of muscle magnetic resonance imaging of a large cohort of patient with VCP-mediated disease reveals characteristic features useful for diagnosis.

Background: The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far.

Methods: We collected muscle MRIs of 80 of the 255 patients who participated in the "VCP International Study" and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences.

Technical aspects and current clinical applications of the skin and skeletal muscle biopsy in neurological diagnostics: an overview.

This short overview recalls the basic principles and technical aspects of skin and skeletal muscle biopsies in humans with paying special attention to the stages of these procedures essential for further correct morphological diagnosis. Some of these principles may also be useful in animal experimental studies. The authors emphasize the important role of proper thickness of the skin fragment, proper orientation of muscle fibres and a scalpel during skin biopsy, and proper concentration of fixatives.

Comprehensive non-invasive assessment of electrocardiographic abnormalities and cardiac arrhythmias in patients with genetically confirmed mitochondrial diseases.

Background: There is limited data on cardiac arrhythmias and ventricular repolarization and dispersion abnormalities in patients with mitochondrial diseases (MitD).

Methods: Consecutive 40 patients with genetically proven MitD and 35 healthy controls were studied. Among other examinations all subjects underwent 24-h Holter recording and 12‑lead electrocardiography (ECG) with corrected QT (QTc), QT dispersion (QTd), Tp-e and Tp-e/QT ratio assessment.

Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.

Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO.

Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC).

Background: The European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) was launched to register rare muscle glycogenoses in Europe, to facilitate recruitment for research trials and to learn about the phenotypes and disseminate knowledge about the diseases through workshops and websites. A network of twenty full and collaborating partners from eight European countries and the US contributed data on rare muscle glycogenosis in the EUROMAC registry. After approximately 3 years of data collection, the data in the registry was analysed.

Meningitis and Ramsay-Hunt syndrome in a 17-year old girl.

Introduction: Ramsay Hunt syndrome (RHS) is a rare manifestation of varicella-zoster virus (VZV) reactivation in geniculate ganglion. It usually manifests with a characteristic triad of symptoms including ipsilateral ear pain, vesicles in the external auditory canal, and facial nerve palsy.

Case: We present a case report showing RHS additionally manifested by meningitis and involvement of VIII cranial nerve.

Screening for late-onset Pompe disease in Poland.

Objectives: We aimed to screen for late-onset Pompe disease using the dried blood spot (DBS) test in a cohort of patients with limb-girdle muscle weakness or persistent hyperCKemia.

Materials And Methods: Patients with limb-girdle muscle weakness, persistently elevated CK, rigid spine syndrome, dyspnoea, myalgia or sibling of the patient diagnosed with LOPD were included in the study. Acid α-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry and followed by genetic testing when required.

The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort.

Diseases related to DNA polymerase gamma dysfunction comprise of heterogeneous clinical presentations with variable severity and age of onset. Molecular screening for the common POLG variants: p.Ala467Thr, p.

Ultrastructural changes in microvessels in familial hemiplegic migraine with mutation.

Aims: Familial hemiplegic migraine type 1 (FHM1) due to mutations in the gene is known as functional vascular disorder with cerebellar atrophy. We describe a case of a FHM1 family in which pathological changes occurred in both brain neuroimaging and skin and muscle biopsy.

Materials And Methods: In 5 of 18 affected family members, brain MRI scans revealed hyperintense changes in the cerebral white matter.

Comprehensive evaluation of EMG and biopsy findings supported by computer simulations - A preliminary study.

Objective: The aim was to compare muscle fiber diameters obtained from standard muscle biopsy and from computer simulations based on recorded motor unit potentials (MUPs).

Methods: Electromyography (EMG) and muscle biopsy were performed in 14 patients with a suspicion of a neuromuscular disorder. Histograms of the simulated muscle fiber diameters (SMFDs) were compared with those from the biopsy RESULTS: The values of the SMFDs were similar to those in the muscle biopsy for the same patient (p = 0.

A synergistic effect of phosphate, pH and Phe159 substitution on the formycin A association to the E. coli purine nucleoside phosphorylase.

A steady-state absorption and emission spectroscopy was used to create a comprehensive work and to study the interaction of the wild type Escherichia coli purine nucleoside phosphorylase and its mutants, PNPF159Y and PNPF159A, with a potent E. coli PNP inhibitor - formycin A. The absorption and emission spectra were recorded in the presence and absence of the phosphate at the 50 mM concentration.

Electromyographic findings in sporadic inclusion body myositis.

Introduction: Clinically oriented diagnostic criteria can be as specific for diagnosis of sporadic inclusion body myositis (sIBM) as pathological criteria, especially at the time of presentation. EMG may provide an convincing proof that a muscle biopsy should be performed.

Aims: To compare the EMG results in patients with sIBM divided into subgroups based on the newest ENMC criteria for sIBM and to obtain the utility of EMG in the diagnostic process at the time of presentation.

Towards understanding the E. coli PNP binding mechanism and FRET absence between E. coli PNP and formycin A.

The aim of this study is threefold: (1) augmentation of the knowledge of the E. coli PNP binding mechanism; (2) explanation of the previously observed 'lack of FRET' phenomenon and (3) an introduction of the correction (modified method) for FRET efficiency calculation in the PNP-FA complexes. We present fluorescence studies of the two E.

Identification of the first in Poland CACNA1A gene mutation in familial hemiplegic migraine. Case report.

Introduction: Migraine is a common neurological disorder characterized by a particular phenotype, complex pathophysiology and a heterogeneous genetic background. Among several heritable forms, familial hemiplegic migraine is the best described one. In the majority of cases it is caused by mutations in one of three different genes.

Abnormal spontaneous activity in primary myopathic disorders.

Introduction: Reproducible non-insertional spontaneous activity (SA), with the exception of endplate activity, is an unequivocal sign of abnormality and is one of the most useful findings obtained on electromyography.

Methods: In this retrospective study we analyzed occurrence and distribution of abnormal SA in 151 patients with genetically confirmed myopathies.

Results: Complex repetitive discharges (CRDs) occurred more frequently than fibrillation potentials (fibs) and positive sharp waves (PSWs) in centronuclear myopathy (CNM) and limb-girdle muscular dystrophy type 2A (LGMD-2A), whereas fibs/PSWs were observed more often in desminopathy and facioscapulohumeral dystrophy (FSHD).

Phosphorylation of thymidylate synthase affects slow-binding inhibition by 5-fluoro-dUMP and N(4)-hydroxy-dCMP.

Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic or linear dependence of the inactivation rate on time and accompanied by differing inhibition parameters. Considering its importance for chemotherapeutic drug resistance, the possible effect of thymidylate synthase inhibition by post-translational modification was tested, e.

Sporadic inclusion body myositis: clinical, pathological, and genetic analysis of eight Polish patients.

Introduction: Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in patients above 50 years of age. Its progressive course finally leads to immobilisation, and no effective therapy exists. Its pathogenesis includes both degenerative and inflammatory processes, however, its direct causes remain unknown.

[Role of tautomerism in the molecular mechanisms of mutagenesis].

Environment of human being usually contains a high number of environmental mutagens, which may modify chemically nucleic acid bases into promutagenic analogues. Hydroxylamine (NH2OH) is a strong mutagen which modifies cytosine and adenine to N4-hydroxycytosine and N6-hydroxyadenine, respectively. Once these analogues are present in DNA or RNA, they may cause transition point mutations by the exchange between two pairs C:G and A:T into T:A and G:C, respectively.

Yeast model analysis of novel polymerase gamma variants found in patients with autosomal recessive mitochondrial disease.

Replication of the mitochondrial genome depends on the single DNA polymerase (pol gamma). Mutations in the POLG gene, encoding the catalytic subunit of the human polymerase gamma, have been linked to a wide variety of mitochondrial disorders that show remarkable heterogeneity, with more than 200 sequence variants, often very rare, found in patients. The pathogenicity and dominance status of many such mutations remain, however, unclear.

A QM-MD simulation approach to the analysis of FRET processes in (bio)molecular systems. A case study: complexes of E. coli purine nucleoside phosphorylase and its mutants with formycin A.

Predicting FRET pathways in proteins using computer simulation techniques is very important for reliable interpretation of experimental data. A novel and relatively simple methodology has been developed and applied to purine nucleoside phosphorylase (PNP) complexed with a fluorescent ligand - formycin A (FA). FRET occurs between an excited Tyr residue (D*) and FA (A).