Correlating motor unit morphology with bioelectrical activity - A simulation study.

Objectives: The aim was to determine motor unit morphology underpinning the various MUP waveforms using MUP analysis.

Method: The simulation method is based on the decomposition of MUP into single fiber potentials. Number of fibers, fiber diameters and fiber to electrode distances were determined.

Dysfunctional lamins as mediators of oxidative stress in Emery-Dreifuss muscular dystrophy.

Deficit of lamin A/C or emerin causes genetically transmitted Emery-Dreifuss muscular dystrophy (EDMD). As lamins are considered to be mediators of oxidative stress, the antioxidant/oxidant status was examined. The total oxidant/antioxidant status in serum was examined in 29 cases of Emery-Dreifuss muscular dystrophy.

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

Background: Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies.

Limb-girdle muscular dystrophy with severe heart failure overlapping with lipodystrophy in a patient with LMNA mutation p.Ser334del.

Laminopathies, a group of heterogeneous disorders associated with lamin A/C gene (LMNA) mutations, encompass a wide spectrum of clinical phenotypes, which may present as separate disease or as overlapping syndromes. We describe a 35-year-old female in whom a novel sporadic heterozygous mutation c.1001_1003delGCC (p.

Novel Col12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects.

Introduction: Mutations in the COL12A1 (collagen, type XII, alpha 1) gene have been described in a milder Bethlem-like myopathy in 6 patients from 3 families (dominant missense), and in a severe congenital form with failure to attain ambulation in 2 patients in a single pedigree (recessive loss-of-function).

Methods: We describe an 8-year-old girl of Polish origin who presented with profound hypotonia and joint hyperlaxity at birth after a pregnancy complicated by oligohydramnios and intrauterine growth retardation.

Results: We identified a novel, potentially pathogenic heterozygous missense COL12A1 c.

Cardiac pacing in 21 patients with Emery-Dreifuss muscular dystrophy: a single-centre study with a 39-year follow-up.

Background: Emery-Dreifuss muscular dystrophy (EDMD) is a genetic condition associated with cardiac arrhythmias. The patients typically develop early, asymptomatic bradyarrhythmia, which may lead to sudden death, preventable with a cardiac implantable electronic device (CIED). EDMD may be characterised by atrial electrical silence.

The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.

Background: Limb girdle muscular dystrophy 2A (LGMD2A) is the most frequent LGMD variant in the European population, representing about 40% of LGMD. The c.550delA mutation in the CANP3 (calcium activated neutral protease 3) gene is the most commonly reported mutation in LGMD2A.

Emery-Dreifuss muscular dystrophy type 2 associated (?) with mild peripheral polyneuropathy.

In recent years numerous mutations in the LMNA gene encoding lamin A/C were shown to segregate with a wide spectrum of phenotypes. A recurrent p.R377H mutation in the LMNA gene was reported in patients with Emery-Dreifuss dystrophy (EDMD2) with various ethnic backgrounds.

Tissue inhibitors of matrix metalloproteinases in serum are cardiac biomarkers in Emery-Dreifuss muscular dystrophy.

Background: Tissue inhibitors of matrix metalloproteinases (TIMPs) are known to be involved in cardiovascular diseases. Hitherto, they have not been examined in dilated cardiomyopathy in the course of Emery-Dreifuss muscular dystrophy (EDMD).

Aim: To define TIMPs in serum because they might help in defining cardiac dysfunction at the early cardiological stages of this disease and detect preclinical stages of cardiomyopathy.

The LITAF/SIMPLE I92V sequence variant results in an earlier age of onset of CMT1A/HNPP diseases.

Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) represent the most common heritable neuromuscular disorders. Molecular diagnostics of CMT1A/HNPP diseases confirm clinical diagnosis, but their value is limited to the clinical course and prognosis. However, no biomarkers of CMT1A/HNPP have been identified.

A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation.

Charcot-Marie-Tooth (CMT) disease caused by mutations in the GDAP1 gene has been shown to be inherited via traits that may be either autosomal recessive (in the majority of cases) [CMT4A] or autosomal dominant [CMT2K]. CMT4A disease is characterized by an early onset, and a severe clinical course often leading to a loss of ambulation, whereas CMT2K is characterized by a mild clinical course of benign axonal neuropathy beginning even in the 6th decade of life. Clinical data from a GDAP1 mutated patient suggests that the presence of a particular mutation is associated with a certain trait of inheritance.

Novel point mutations in survival motor neuron 1 gene expand the spectrum of phenotypes observed in spinal muscular atrophy patients.

The aim of our study was to identify point mutations in a group of 606 patients diagnosed for spinal muscular atrophy with excluded biallelic loss of the SMN1 gene. Point missense mutations or small deletions in the SMN1 gene were ultimately identified in 18 patients. Six patients were found to have small deletions, the c.

A late-onset and mild form of Charcot-Marie-Tooth disease type 2 caused by a novel splice-site mutation within the Mitofusin-2 gene.

Charcot-Marie-Tooth type 2A disease (CMT2A) caused by mutations in the Mitofusin 2 gene (Mfn2) has been shown to be an early-onset axonal neuropathy with severe clinical course in the majority of the patients. In this study we present a unique phenotype of CMT2A disease characterized by late-onset polyneuropathy with a very mild clinical course. This rare form of CMT2A disease is caused by a new splice-site (c.

Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features.

Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes.

Severe phenotypes of SMARD1 associated with novel mutations of the IGHMBP2 gene and nuclear degeneration of muscle and Schwann cells.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth.

Is mutation p.Arg168Gly in TPM3 gene responsible for Type 1 fiber hypoplasia and cap structure formation?

Congenital fiber type disproportion with delayed fiber type maturation and the appearance of cap structures were analyzed in a child with p.Arg168Gly mutation in TPM3 gene. Very narrow myotube-like Type 1 fibers with single nuclei decorated by cap structures seem to be a result of a failure in fusion process and mature fiber formation.

Advances in basic and clinical research in laminopathies.

Lamins (LMNA) are the main proteins of the nuclear lamina considered to be the ancestors of all intermediate filament proteins. They form complex protein assemblies with integral proteins of the inner nuclear membrane, transcriptional regulators, histones and chromatin modifiers. During recent years, interest in lamins has greatly increased due to the identification of many distinct heritable human disorders associated with lamin mutations.

Relationships between clinical data and quantitative EMG findings in facioscapulohumeral muscular dystrophy.

Background And Purpose: In recently published reports, electrophysiological findings were analysed, in some facioscapulo-humeral muscular dystrophy (FSHD) cases without genetic disease confirmation. In several reports, some electrophysiological findings were described, not specific for myopathy. The aim of study was to analyse electrophysiological findings in a genetically homogeneous FSHD group to find possible relationships between electromyography (EMG) abnormalities and clinical symptoms.

Motor unit potentials with satellites in dystrophinopathies.

Introduction: The objective of this study was to analyze the motor unit potentials (MUPs) with satellite components i.e., delayed by at least 2ms baseline from the main component, in the dystrophinopathies.

Regional and transmural dispersion of repolarisation in patients with Emery-Dreifuss muscular dystrophy.

Background: The development of malignant ventricular arrhythmias is a possible feature in Emery-Dreifuss muscular dystrophy (EDMD) patients with normal left ventricular systolic function. This event may be the cause of sudden cardiac death in EDMD patients. QTc dispersion (QTc-D), JTc dispersion (JTc-D) and Tpeak-end dispersion (TDR) could reflect the physiological variability of regional and transmural ventricular repolarisation and could provide a substrate for life-threatening ventricular arrhythmias.

A method for determination of muscle fiber diameter using single fiber potential (SFP) analysis.

We have used computer simulation to study the relationship between the muscle fiber diameter and parameters: peak-to-peak amplitude and duration of the negative peak of the muscle fiber action potential. We found that the negative peak duration is useful in the determination of fiber diameter via the diameter dependence of conduction velocity. We have shown a direct link between the underlying physiology and the measurements characterizing single fiber potential.