Laura Rufibach
A5053390029- Muscle Physiology and Disorders
- Nutrition and Health in Aging
- Neurogenetic and Muscular Disorders Research
- Body Contouring and Surgery
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Adipose Tissue and Metabolism
- Muscle activation and electromyography studies
- RNA Research and Splicing
- Diagnosis and Treatment of Venous Diseases
- Genomics and Rare Diseases
- Nuclear Structure and Function
- Children's Physical and Motor Development
- Inflammatory Myopathies and Dermatomyositis
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- Telomeres, Telomerase, and Senescence
- Tissue Engineering and Regenerative Medicine
- Body Composition Measurement Techniques
- Genetics and Neurodevelopmental Disorders
- Mitochondrial Function and Pathology
- Systemic Sclerosis and Related Diseases
- Extracellular vesicles in disease
- Exercise and Physiological Responses
- Obstructive Sleep Apnea Research
Jain Foundation
2015-2024
Seattle University
2015-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2023
Newcastle University
2016-2019
Institute for Advanced Medical Research
2017
Bellevue Hospital Center
2009-2013
University of Washington Medical Center
2006
Abstract Objective Limb‐girdle muscular dystrophies ( LGMD s), one of the most heterogeneous neuromuscular disorders NMD involves predominantly proximal‐muscle weakness with >30 genes associated different subtypes. The clinical‐genetic overlap among subtypes and other s complicate disease‐subtype identification lengthening diagnostic process, increases overall costs hindering treatment/clinical‐trial recruitment. Currently seven clinical trials are active but still no gene‐therapy‐related...
Background and objective Dysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous imaging studies describe selective pattern involvement smaller patient cohorts, but large study across entire spectrum dysferlinopathies had not been performed previous findings were correlated with functional tests. Methods We present cross-sectional T1-weighted MRI data from 182 patients genetically confirmed dysferlinopathies. have analysed muscles involved disease...
<h3>Objective:</h3> To describe the baseline clinical and functional characteristics of an international cohort 193 patients with dysferlinopathy. <h3>Methods:</h3> The Clinical Outcome Study for dysferlinopathy (COS) is multicenter study this disease, evaluating genetically confirmed over 3 years. We present a cross-sectional analysis derived from their assessments. <h3>Results:</h3> There high degree variability in disease onset, pattern weakness, rate progression. No factor, such as...
Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British German LGMD2L patients so far reported. We aimed further investigate prevalence spectrum mutations related clinical phenotypes, screening 205 undiagnosed referred our molecular service with suspicion anoctaminopathy....
Objective: Inherited myopathies comprise more than 200 different individually rare disease-subtypes, but when combined together they have a high prevalence of 1 in 6,000 individuals across the world. Our goal was to determine for first time clinical- and gene-variant spectrum genetic substantial cohort study Indian subcontinent. Methods: In this study, we performed large clinical exome sequencing (ES) with phenotype correlation on 207 clinically well-characterized inherited...
This study aims to determine clinically relevant phenotypic differences between the two most common classifications in dysferlinopathy, limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MMD1). LGMDR2 MMD1 are reported involve different muscles, with showing predominant weakness distal lower weakness. We used heatmaps, regression analysis principle component of functional Magnetic Resonance Imaging data perform a cross-sectional review pattern muscle involvement 168 patients...
Mutations in the dysferlin gene (DYSF) lead to a complete or partial absence of protein skeletal muscles and are at origin dysferlinopathies, heterogeneous group rare autosomal recessive inherited neuromuscular disorders. As step towards better understanding DYSF mutational spectrum, possible inclusion patients future therapeutic clinical trials, we set up Universal Mutation Database for Dysferlin (UMD-DYSF), Locus-Specific developed with UMD® software. The main objective UMD-DYSF is provide...
Objective Dysferlinopathy is a muscular dystrophy with highly variable clinical presentation and currently unpredictable progression. This variability unpredictability presents difficulties for prognostication trial design. The Jain Clinical Outcomes Study of aims to establish the validity North Star Assessment Limb Girdle Type Muscular Dystrophies (NSAD) scale identify factors that influence rate disease progression using NSAD. Methods We collected longitudinal series functional assessments...
Abstract Background Water T2 (T2 H2O ) mapping is increasingly being used in muscular dystrophies to assess active muscle damage. It has been suggested as a surrogate outcome measure for clinical trials. Here, we investigated the prognostic utility of identify changes function over time limb girdle dystrophies. Methods Patients with genetically confirmed dysferlinopathy were assessed part Jain Foundation Clinical Outcomes Study dysferlinopathy. The cohort included 18 patients from two sites,...
Abstract Introduction/Aims There is debate about whether and to what extent either respiratory or cardiac dysfunction occurs in patients with dysferlinopathy. This study aimed establish definitively system part of the dysferlinopathy phenotype. Methods As Jain Foundation's International Clinical Outcome Study (COS) for dysferlinopathy, objective measures function were collected twice, a 3‐y interval between tests, 188 genetically confirmed aged 11–86 y (53% female). Measures included forced...
Hepatic lipase (HL) plays a key role in the metabolism of plasma lipoproteins, and its level activity requires tight regulation, given association both low high levels with atherosclerosis coronary artery disease. However, little is known about factors responsible for HL expression. Here, we report that human hepatic gene (LIPC) promoter regulated by hepatocyte nuclear factor 4alpha (HNF4alpha), peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), apolipoprotein...
To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.One hundred ninety-three patients with were recruited Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, hand-held...
Abstract Objective Dysferlin is a large transmembrane protein that functions in critical processes of membrane repair and vesicle fusion. Dysferlin‐deficiency due to mutations the dysferlin gene leads muscular dystrophy (Miyoshi myopathy ( MM ), limb girdle type 2B LGMD 2B), distal with anterior tibial onset DMAT )), typically early adult onset. At least 416 pathogenic are known, but for approximately 17% patients, one or both their variants remain undefined following standard exon...
Dysferlin deficiency causes dysferlinopathies. Among peripheral blood mononuclear cells (PBMCs), the dysferlin protein is expressed specifically in CD14(+) monocytes.We quantified levels PBMC lysates of 77 individuals suspected clinically having a dysferlinopathy to screen for true positives. Subsequent molecular confirmation was done by Sanger sequencing and comparative genomic hybridization arrays establish diagnosis.Of 44 who had significantly reduced (≤10%), 41 underwent testing. We...
Background: Limb-girdle muscular dystrophy (LGMD) is the most common adult-onset class of dystrophies in India, but a majority suspected LGMDs India remain unclassified to genetic subtype level. The next-generation sequencing (NGS)-based approaches have allowed molecular characterization and diagnosis these patients India. Materials Methods: (I) To select probable dysferlinopathy (LGMD2B) cases from other LGMD subtypes using two screening methods (i) determine status dysferlin protein...
Dysferlinopathies are muscular dystrophies caused by recessive loss-of-function mutations in dysferlin (
Myostatin is a myokine which acts upon skeletal muscle to inhibit growth and regeneration. endogenously antagonised by follistatin. This study assessed serum myostatin follistatin concentrations as monitoring or prognostic biomarkers in dysferlinopathy, an autosomal recessively inherited muscular dystrophy. was quantified twice with three-year interval 76 patients dysferlinopathy 38 controls. Follistatin 62 of these at the same timepoints, 31 Correlations motor function, fat fraction...
Abstract Objective Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree phenotypic homogeneity. LGMD is defined as having onset >2 years age progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to surge genes linked LGMD. Methods The ClinGen Muscular Dystrophies Myopathies gene curation expert panel (MDM GCEP,...
Dysferlinopathy is a muscular dystrophy with highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims identify suitability PROMs and their association motor performance.Two-hundred four patients dysferlinopathy were identified Jain Foundation's Clinical Outcome Study from 14 sites 8 countries. All completed following PROMs: Individualized Neuromuscular Quality...