A5072777117- Cardiomyopathy and Myosin Studies
- Genomics and Rare Diseases
- Muscle Physiology and Disorders
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Connective tissue disorders research
- Nuclear Structure and Function
- Congenital heart defects research
- Genetic Syndromes and Imprinting
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Skin and Cellular Biology Research
- Ion channel regulation and function
- Cardiovascular Effects of Exercise
- Genetic factors in colorectal cancer
- Fibroblast Growth Factor Research
- Caveolin-1 and cellular processes
- Inflammatory Myopathies and Dermatomyositis
- Drilling and Well Engineering
- Medical and Biological Sciences
- Vascular Malformations and Hemangiomas
- Chromosomal and Genetic Variations
Radboud University Nijmegen
2024-2025
Radboud University Medical Center
2024-2025
University of Helsinki
2017-2023
Folkhälsans Forskningscentrum
2016-2023
University of the Basque Country
2017
Biogipuzkoa Health Research Institute
2017
Tampere University
2017
Vaasa Central Hospital
2017
Abstract Solve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilised 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural (SVs), single nucleotide (SNVs), insertion-deletions (InDels), and short tandem repeat (STR) expansions extensively studied families without clear molecular diagnoses. Our cohort includes 293 individuals from 114 genetically selected...
Abstract Background myotilinopathy is a very rare inherited muscle disease that belongs to the group of myofibrillar myopathies. These diseases share common alteration sarcomere organization at level Z disk resulting in pathological protein aggregation, autophagic abnormalities, and ultimately degeneration. Most reported cases are due dominant missense mutations MYOT gene, two which largely recurrent. Methods We describe clinical, radiological, pathological, molecular analysis including...
Solve-RD is a pan-European rare disease (RD) research program that aims to identify disease-causing genetic variants in previously undiagnosed RD families. We utilized 10-fold coverage HiFi long-read sequencing (LRS) for detecting causative structural (SVs), single-nucleotide (SNVs), insertion-deletions (indels), and short tandem repeat (STR) expansions studied families without clear molecular diagnosis. Our cohort includes 293 individuals from 114 genetically selected by European Reference...
Background and purpose Nemaline myopathy (NEM) has been associated with mutations in 12 genes to date. However, for some patients diagnosed NEM, definitive are not identified the known genes, suggesting that there other involved. This study describes compound heterozygosity rare variants ryanodine receptor type 3 ( RYR ) gene one such patient. Methods results Clinical examination of patient at 22 years age revealed a long narrow face, high arched palate bilateral facial weakness. She had...
Bioinformatics tools for analyzing copy number variants (CNVs) from massively parallel sequencing (MPS) data are less well developed compared with other variant types. We present an efficient bioinformatics pipeline CNV detection gene panel MPS in neuromuscular disorders. CNVs were generated silico into samples sequenced a previously published panel. The these analyzed four programs having complementary ranges: CoNIFER, XHMM, ExomeDepth, and CODEX. A logistic regression model was trained the...
<h3>Objective:</h3> Copy number variants (CNVs) were analyzed from next-generation sequencing data, with the aim of improving diagnostic yield in skeletal muscle disorder cases. <h3>Methods:</h3> Four publicly available bioinformatic analytic tools used to analyze CNVs data patients diseases. The previously a targeted gene panel for single nucleotide and small insertions deletions, without achieving final diagnosis. Variants detected by multiple CNV analysis verified either array comparative...
Our previous array, the Comparative Genomic Hybridisation design (CGH-array) for nemaline myopathy (NM), named NM-CGH revealed pathogenic copy number variation (CNV) in genes nebulin (NEB) and tropomyosin 3 (TPM3), as well recurrent CNVs segmental duplication (SD), i.e. triplicate, region of NEB (TRI, exons 82-89, 90-97, 98-105). In light this knowledge, we have designed validated an extended CGH which includes a selection 187 known to cause neuromuscular disorders (NMDs).Our aim was develop...
ABSTRACT Introduction : Nebulin is a giant actin‐binding protein in the thin filament of skeletal muscle sarcomere. Studies nebulin interactions are limited by size, complexity, and poor solubility protein. We divided super‐repeat region into panel, studied nebulin/actin interactions. Methods Actin binding was using co‐sedimentation assay with filamentous actin 26 different super‐repeats. Results The panel revealed notable differences between Both ends bound significantly more strongly,...
Nemaline Myopathy (NM) is a rare genetic disorder that encompasses large spectrum of myopathies characterized by hypotonia and generalized muscle weakness. To date, mutations in thirteen different genes have been associated with NM. The most frequently responsible are NEB (50% cases) ACTA1 (15–25% cases). In this report all known NM related were screened Next Generation Sequencing five Spanish patients order to genetically confirm the clinical histological diagnosis Four (c.17779_17780delTA,...
Pathogenic variants in the TPM3 gene, encoding slow skeletal muscle α-tropomyosin account for less than 5% of nemaline myopathy cases. Dominantly inherited or de novo missense are more common recessive loss-of-function variants. The reported to date seem affect either 5' 3' end muscle-specific transcript.The aim study was identify disease-causing gene and a Finnish patient with an unusual form myopathy.The genetic analyses included Sanger sequencing, whole-exome targeted array-CGH,...
The human genome contains repetitive regions, such as segmental duplications, known to be prone copy number variation. Segmental duplications are highly identical and homologous sequences, posing a specific challenge for most mutation detection methods. giant nebulin gene is expressed in skeletal muscle. It harbors large duplication region composed of eight exons repeated three times, the so-called triplicate region. Mutations cause nemaline myopathy other congenital myopathies. Using our...
Abstract Introduction Structural variants (SVs) of the nebulin gene ( NEB ), including intragenic duplications, deletions, and copy number variation triplicate region, are an established cause recessively inherited nemaline myopathies related neuromuscular disorders. Large deletions have been shown to dominantly distal myopathies. Here we provide overview 35 families with muscle disorders caused by such SVs in . Methods Using custom Comparative Genomic Hybridization arrays, exome sequencing,...
Abstract Intragenic segmental duplication regions are potential hotspots for recurrent copy number variation and possible pathogenic aberrations. Two large sarcomeric genes, nebulin titin, both contain such regions. Using our custom Comparative Genomic Hybridization array, we have previously shown that a gain or loss of more than one the repeated block triplicate region constitutes recessive mutation. targeted array-CGH, similar variants can be detected in titin. Due to limitations array-CGH...