A5011689193- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Amyotrophic Lateral Sclerosis Research
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- RNA regulation and disease
- RNA modifications and cancer
- Prostate Cancer Treatment and Research
- Neurological diseases and metabolism
- Connective tissue disorders research
- Heat shock proteins research
- Hereditary Neurological Disorders
- Skin and Cellular Biology Research
- Inflammatory Myopathies and Dermatomyositis
- Endoplasmic Reticulum Stress and Disease
- Prostate Cancer Diagnosis and Treatment
- Cardiac and Coronary Surgery Techniques
- Ear and Head Tumors
- Ion channel regulation and function
Tampere University
2014-2024
Screen
2024
Fimlab (Finland)
2014-2024
Tampere University Hospital
2014-2024
University of Helsinki
2015-2021
Ospedale Papa Giovanni XXIII
2021
King's College London
2021
Vaasa Central Hospital
2010-2021
Turku University Hospital
2019-2021
Telethon Institute Of Genetics And Medicine
2021
To report novel disease and pathology due to HSPB8 mutations in 2 families with autosomal dominant distal neuromuscular showing both myofibrillar rimmed vacuolar myopathy together neurogenic changes.We performed whole-exome sequencing (WES) tandem linkage analysis candidate gene approach as well targeted next-generation (tNGS) identify causative a motor neuropathy. Pathogenic variants familial segregation were confirmed using Sanger sequencing.WES tNGS identified heterozygous change...
Mutations in the titin gene (TTN) cause a large spectrum of diseases affecting skeletal and/or cardiac muscle. TTN includes 363 coding exons, repeated region with high degree complexity, isoform-specific elements, and metatranscript-only exons thought to be expressed only during fetal development. Although three main classes isoforms have been described so far, alternative splicing events (ASEs) different tissues or developmental physiological states reported. To achieve comprehensive view...
Abstract Several alternative techniques exist to reconstruct skull defects. The complication rate of the cranioplasty procedure is high and search for optimal materials continues. To report long-term results patients who have received a using autologous adipose-derived stem cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between 10/2008 3/2010, five cranioplasties were performed (four females, one male; average age 62.0 years) ASCs, betaTCP granules titanium or...
Nemaline myopathy (NM) is one of the most common non-dystrophic genetic muscle disorders. NM often associated with mutations in NEB gene. Even though exact NEB-NM pathophysiological mechanisms remain unclear, histological analyses patients' biopsies reveal unexplained accumulation glycogen and abnormally shaped mitochondria. Hence, aim present study was to define molecular cellular cascade events that would lead potential changes energetics NEB-NM. For that, we applied a wide range...
Limb girdle muscular dystrophies are a large group of both dominantly and recessively inherited muscle diseases. LGMD1D is caused by mutated DNAJB6 the molecular pathogenesis mediated defective chaperonal function leading to impaired handling misfolded proteins which normally would be degraded. Here we aim clarify pathology in order facilitate diagnostic accuracy. After following six Finnish families, analysed 21 biopsies obtained from 15 patients at different time points after onset...
Abstract Objective Inclusion body myositis (IBM) has an unclear molecular etiology exhibiting both characteristic inflammatory T-cell activity and rimmed-vacuolar degeneration of muscle fibers. Using in-depth gene expression splicing studies, we aimed at understanding the different components pathomechanisms in IBM. Methods We performed RNA-seq on RNA extracted from skeletal biopsies clinically histopathologically defined IBM ( n = 24), tibial muscular dystrophy 6), normal group 9). In a...
Limb-girdle muscular dystrophy 2J caused by mutations in C-terminal titin has so far been identified Finnish patients only. This may part be due to limited availability of diagnostic tests for defects. In this report, a French family with an autosomal-dominant late-onset distal myopathy the tibial phenotype segregating several members was described. One deceased patient proved homozygous truncating mutation because consanguinity. According available medical records, had clearly more severe...
The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed biopsy 23 patients with autosomal dominant lower disease caused by p.G66V mutation CHCHD10 (SMAJ), 10 X-linked spinal bulbar muscular atrophy (SBMA) 11 c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting non-atrophic IIA fibers were 100% specific for the late-onset...
Nebulin is a large actin-binding protein of the skeletal muscle sarcomere. Multiple isoforms nebulin are produced from 183-exon-containing gene (NEB). Mutations in NEB cause nemaline myopathy, distal and core-rod myopathy.Nebulin mRNA expression was assessed by microarrays RT-PCR 21 human leg 2 brain samples. Protein immunohistochemistry 5 regions 1 sample.Nebulin isoform diversity as high muscle. Isoforms with more than 22 super repeats seem to be common previously anticipated....
<h3>Introduction</h3> Two families with autosomal dominant limb girdle muscular dystrophy (LGMD) have previously been linked to a locus on chromosome 7q36 10 years ago. The has termed both LGMD1D and 1E, but because of lack additional narrow down the region interest, this disease remained elusive. <h3>Methods</h3> A large Finnish family was clinically genetically investigated. Laboratory parameters were determined, including creatine kinase (CK) value, neurographic electromyography studies,...
To describe adult-onset limb-girdle-type muscular dystrophy caused by biallelic variants in the PYROXD1 gene, which has been recently linked to early-onset congenital myofibrillar myopathy.Whole exome sequencing was performed for neuromuscular disease patients with no molecular diagnosis. Patients underwent clinical characterization, lower limb muscle MRI, biopsy and spirometry. A yeast complementation assay used determine biochemical consequences of genetic variants.We identified four...
To identify the genetic defect causing a distal calf myopathy with cores.Families genetically undetermined calf-predominant underwent detailed clinical evaluation, including EMG/nerve conduction studies, muscle biopsy, laboratory investigations, and MRI. Next-generation sequencing targeted Sanger were used to causative in each family.A novel deletion-insertion mutation ryanodine receptor 1 (RYR1) was found proband of index family segregated disease 6 affected relatives. Subsequently, we 2...
Characterization of a new type late-onset autosomal dominant lower motor neuron disease.Patients from 2 families underwent detailed neurologic, electrophysiologic, muscle biopsy, and laboratory investigations. MRI limbs was performed in selected patients. DNA samples leukocytes were used for molecular genetic linkage studies.First symptoms cramps fasciculations after age 25-30, followed by slowly progressive proximal distal weakness without overt atrophy during the first decades symptoms....
Tibial muscular dystrophy (TMD) is a late onset, autosomal dominant distal myopathy that results from mutations in the two last domains of titin. The cascade molecular events leading causative Titin to preterm death muscle cells TMD largely unknown. In this study we examined mRNA and protein changes associated with myopathology TMD. To identify these components performed gene expression profiling using biopsies patients healthy controls. were confirmed through quantitative real-time PCR...
Abstract Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked ( SMPX ) gene. Four different missense were ten patients from nine families five countries, suggesting that this disease could be prevalent other populations as well. Haplotype analysis with similar ancestry revealed two founder Southern Europe France, indicating prevalence these may higher. In our study all presented...
To elaborate the diagnostic methods used as "gold standard" in one of most common glycogen storage diseases (GSDs), Tarui disease (GSDVII).Two siblings with suggestive GSD underwent thorough clinical analysis, including muscle biopsy, MRI, exercise tests, laboratory examinations, and whole-exome sequencing (WES).Both had juvenile-onset intolerance cramping infrequent myoglobinuria. Muscle biopsy showed extralysosomal accumulation, but because normal phosphofructokinase histochemistry, GSDVII...