Mridul Johari
A5002674217- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genomics and Rare Diseases
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Inflammatory Myopathies and Dermatomyositis
- RNA Research and Splicing
- Nuclear Structure and Function
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Cardiovascular Effects of Exercise
- Glycogen Storage Diseases and Myoclonus
- Mitochondrial Function and Pathology
- Systemic Sclerosis and Related Diseases
- Amyotrophic Lateral Sclerosis Research
- CRISPR and Genetic Engineering
- Neurological diseases and metabolism
- Immunodeficiency and Autoimmune Disorders
- Cellular transport and secretion
- Muscle and Compartmental Disorders
- Eosinophilic Disorders and Syndromes
- Cellular Mechanics and Interactions
Harry Perkins Institute of Medical Research
2023-2025
Folkhälsans Forskningscentrum
2016-2025
The University of Western Australia
2023-2025
University of Helsinki
2013-2025
Vaasa Central Hospital
2017-2024
Weatherford College
2024
Vall d'Hebron Institut de Recerca
2024
European Society of Radiology
2023-2024
Leiden University Medical Center
2024
Maastricht University
2024
Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG) dynamics and autophagic protein degradation that underlie the pathogenesis a spectrum degenerative diseases affect muscle, brain, bone. Specifically, identical mutations in adaptor SQSTM1 can cause varied penetrance 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease bone, distal myopathy. It has been hypothesized clinical pleiotropy relates to additional genetic...
Abstract Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield patients with rare diseases. However, cost and efforts required for reanalysis prevent its routine implementation in research clinical environments. The Solve-RD project aims to reveal molecular causes underlying undiagnosed One goals is implement innovative approaches reanalyse exomes genomes from thousands well-studied cases. raw genomic submitted through RD-Connect Genome-Phenome Analysis...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
Abstract Structural variants (SVs), including large deletions, duplications, inversions, translocations, and more complex events have the potential to disrupt gene function resulting in rare disease. Nevertheless, current pipelines clinical decision support systems for exome sequencing (ES) tend focus on small alterations such as single nucleotide (SNVs) insertions-deletions shorter than 50 base pairs (indels). Additionally, detection interpretation of copy-number (CNVs) are frequently...
Abstract Background Inclusion Body Myositis is an acquired muscle disease. Its pathogenesis unclear due to the co-existence of inflammation, degeneration and mitochondrial dysfunction. We aimed provide a more advanced understanding disease by combining multi-omics analysis with prior knowledge. applied molecular subnetwork identification find highly interconnected subnetworks high degree change in Myositis. These could be used as hypotheses for potential pathomechanisms biomarkers that are...
Abstract Background Highly expressed in skeletal muscles, the gene Obscurin ( i.e. OBSCN) has 121 non-overlapping exons and codes for some of largest known mRNAs human genome. Furthermore, it plays an essential role muscle development function. Mutations OBSCN are associated with several hypertrophic cardiomyopathies muscular disorders. undergoes extensive complex alternative splicing, which is main reason that its splicing regulation cardiac not previously been thoroughly studied. Methods...
Inherited rare skeletal muscle diseases cause weakness and wasting of variable severity. Without a molecular diagnosis, patients often endure prolonged diagnostic journeys, leading to delays in appropriate management the disease. This occurs approximately 60% with diseases. To facilitate reanalysis 278 unsolved patients, we used gene prioritisation tool Exomiser, which standardises analysis by ranking causative variants based on phenotype relevance variant pathogenicity. Before analysis,...
We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (NM_001267550.1:c.39974-11T>G), inherited in trans second pathogenic variant. Muscle-derived RNA studies of three individuals confirmed mis-splicing induced by the c.39974-11T>G variant; in-frame exon 214 skipping or use cryptic 3' effecting frameshift. Confounding interpretation pathogenicity is absence exons 213-217 within described skeletal muscle N2A...
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...
Myopathy refers to a large group of heterogeneous, rare muscle diseases. Bulk RNA-sequencing has been utilized for the diagnosis and research these diseases many years. However, existing valuable sequencing data often lack integration clinical interpretation. In this study, we integrated bulk from 1221 human skeletal muscles (292 with myopathies, 929 controls) both databases our local samples. By applying method similar single-cell analysis, revealed general spectrum diseases, ranging...
Background and purpose The aim was to determine the genetic background of unknown muscular dystrophy in five French families. Methods Twelve patients with limb girdle or distal myopathy were clinically evaluated. Gene mutations identified using targeted exon sequencing mutated DNAJB 6 tested vitro . Results Five presented lower weakness whilst others had proximal presentation a variable rate progression starting at mean age 38.5 years. Two novel (c.284A>T, p.Asn95Ile, two families;...
Abstract Objective Mutations in the prion‐like domain of RNA binding proteins cause dysfunctional stress responses and associated aggregate pathology patients with neurogenic myopathic phenotypes. Recently, mutations ANXA11 have been reported amyotrophic lateral sclerosis multisystem proteinopathy. Here we studied families an autosomal dominant muscle disease caused by :c.118G > T;p.D40Y. Methods We performed deep phenotyping exome sequencing from four large Greek families, including...
Extensive genetic screening results in the identification of thousands rare variants that are difficult to interpret. Because its sheer size, titin gene (TTN) detected frequently any individual. Unambiguous interpretation molecular findings is almost impossible many patients with myopathies or cardiomyopathies.To refine current classification framework for TTN-associated skeletal muscle disorders and standardize TTN variants.We used guidelines issued by American College Medical Genetics...
Abstract Objective Infantile seizures cause great concern for both doctors and parents. In addition to modern neuroimaging genetics, clinical tools helpful in predicting the course of disease are needed. We prospectively studied incidence, electroclinical characteristics etiologies epilepsy syndromes with onset before age 12 months looked prognostic determinants outcome by 24 months. Methods From February 2017 through May 2019, we recruited all eligible infants diagnosed at our unit. Data on...
<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...
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...
Abstract Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety genetic disorders predispose rhabdomyolysis through different pathogenic mechanisms, particularly patients with recurrent episodes. However, cases remain without a diagnosis. Here we present six who presented severe rhabdomyolysis, usually onset teenage years; other features included history myalgia muscle cramps. We identified 10...