Payam Mohassel
A5068073380- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- Cardiomyopathy and Myosin Studies
- Hereditary Neurological Disorders
- Amyotrophic Lateral Sclerosis Research
- Genomics and Rare Diseases
- Inflammatory Myopathies and Dermatomyositis
- Nuclear Structure and Function
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Peripheral Neuropathies and Disorders
- Myasthenia Gravis and Thymoma
- RNA modifications and cancer
- Lysosomal Storage Disorders Research
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Neurological diseases and metabolism
- Osteoarthritis Treatment and Mechanisms
- Tissue Engineering and Regenerative Medicine
- Connective tissue disorders research
- Sphingolipid Metabolism and Signaling
- Developmental Biology and Gene Regulation
- Genetics and Neurodevelopmental Disorders
Johns Hopkins University
2008-2025
Johns Hopkins Medicine
2013-2025
National Institutes of Health
2015-2024
National Institute of Neurological Disorders and Stroke
2015-2024
National Institute of Environmental Health Sciences
2022
University of California, Los Angeles
2022
University of Nevada, Reno
2022
Nashville Oncology Associates
2022
University of Iowa
2022
Jena University Hospital
2022
Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in
Objective Comprehensive clinical characterization of congenital titinopathy to facilitate diagnosis and management this important emerging disorder. Methods Using massively parallel sequencing we identified 30 patients from 27 families with 2 pathogenic nonsense, frameshift and/or splice site TTN mutations in trans . We then undertook a detailed analysis the clinical, histopathological imaging features these patients. Results All had prenatal or early onset hypotonia contractures. None...
<h3>Objective</h3> To determine the prevalence and clinical features of anti-HMGCR myopathy among patients with presumed limb-girdle muscular dystrophy (LGMD) in whom genetic testing has failed to elucidate causative mutations. <h3>Methods</h3> Patients LGMD unrevealing were selected based on a few clinico-pathologic tested for autoantibodies (n = 11). These are peak creatine kinase (CK) greater than 1,000 IU/L at least 3 following features: (1) pattern weakness, (2) selective involvement...
Transcriptome data can facilitate the interpretation of effects rare genetic variants. Here, we introduce ANEVA (analysis expression variation) to quantify variation in gene dosage from allelic (AE) a population. Application Genotype-Tissues Expression (GTEx) showed that this variance estimate is robust and correlated with selective constraint gene. Using these estimates outlier test (ANEVA-DOT) applied AE 70 Mendelian muscular disease patients accuracy detecting genes pathogenic variants...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons. Mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT), which catalyzes first step de novo synthesis sphingolipids (SLs), cause childhood-onset ALS. SPTLC1-ALS variants map to transmembrane domain interacts with ORMDL proteins, negative regulators SPT activity. We show binding holoenzyme complex impaired cells expressing pathogenic alleles, resulting increased SL and...
<h2>Summary</h2><h3>Background</h3> <i>RYR1</i>-related myopathies (<i>RYR1</i>-RM) are caused by pathogenic variants in the <i>RYR1</i> gene which encodes type 1 ryanodine receptor (RyR1). RyR1 is sarcoplasmic reticulum (SR) calcium release channel that mediates excitation-contraction coupling skeletal muscle. sub-conductance, SR leak, reduced expression, and oxidative stress often contribute to <i>RYR1</i>-RM pathogenesis. Loss of RyR1-calstabin1 association, increased open probability...
Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome humans (CFZS; OMIM 254940) reducing but not eliminating function. We characterize MYMK-CFZS as congenital myopathy with marked...
Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with severe, progressive muscular dystrophy, reminiscent oculopharyngeal dystrophy (OPMD) but much earlier onset, caused by heterozygous frameshift the RBP hnRNPA2/B1. All disease-causing mutations abolish native stop codon extend reading frame, creating novel...
Abstract Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they abundant myelin membranes. Serine palmitoyltransferase, enzyme that catalyses rate-limiting reaction sphingolipid synthesis, is composed multiple subunits including an activating subunit, SPTSSA. both essential cytotoxic their synthesis must therefore be tightly regulated. Key to homeostatic regulation ORMDL proteins bound serine...
<h3>Background</h3> The causes of intellectual disability (ID) are diverse and de novo mutations increasingly recognised to account for a significant proportion ID. <h3>Methods results</h3> In this study, we performed whole exome sequencing on large cohort patients with ID or neurodevelopmental delay identified four novel predicted deleterious missense variants in <i>HECW2</i> six probands ID/developmental hypotonia. Other common features include seizures, strabismus, nystagmus, cortical...
Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of triple helical domain collagens. P4HA1 encodes catalytic α(I) subunit main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic mutations family with congenital-onset disorder connective tissue, manifesting as early-onset joint hypermobility, contractures, muscle weakness bone dysplasia well high myopia, evidence clinical improvement motor function over time surviving patient. Similar to...
Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity weakness. Recently, the first de novo mutations in KIF1A were identified patients with an early-onset severe form complicated hereditary paraplegia. We report two additional novel KIF1A, hereby expanding genetic spectrum KIF1A-related Both children presented paraplegia findings optic nerve atrophy, structural brain abnormalities, peripheral neuropathy,...
Abstract Collagen VI-related dystrophies (COL6-RDs) manifest with a spectrum of clinical phenotypes, ranging from Ullrich congenital muscular dystrophy (UCMD), presenting prominent symptoms and characterised by progressive muscle weakness, joint contractures respiratory insufficiency, to Bethlem dystrophy, milder typically recognised later at times resembling limb girdle intermediate phenotypes falling between UCMD dystrophy. Despite pathology features highly suggestive COL6-RD, some...
Objective Autoantibodies against transcription intermediary factor 1γ (TIF1γ) are found in many patients with dermatomyositis (DM). Although TIF1γ is known to play a role the differentiation of other tissues, its functional muscle regeneration has not been elucidated. This study was undertaken explore regulation and this protein during regeneration. Methods expression analyzed human biopsy specimens using immunofluorescence microscopy. Immunofluorescence microscopy immunoblotting analyses...
In the vertebrate limb over 40 muscles are arranged in a precise pattern of attachment via muscle connective tissue and tendon to bone provide an extensive range motion. How development somite-derived is coordinated with lateral plate-derived tissue, assemble functional musculoskeletal system long-standing question. Mutations T-box transcription factor, TBX3, have previously been identified as genetic cause ulnar-mammary syndrome (UMS), characterized by distinctive defects posterior forelimb...
MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype–phenotype spectrum remains to be explored, pathogenic variants in have recently been reported small number of patients presenting with phenotype cerebellar ataxia, congenital muscle involvement histologic findings ranging from myopathic dystrophic and pigmentary retinopathy. The proposed underlying mechanism MSTO1-related disease is suggestive impaired secondary loss function Disorders...
<h3>Objective</h3> To identify the rate of change clinical outcome measures in children with 2 types congenital muscular dystrophy (CMD), COL6-related dystrophies (COL6-RDs) and LAMA2-related (LAMA2-RDs). <h3>Methods</h3> Over course 4 years, 47 individuals (23 COL6-RD 24 LAMA2-RD) to 22 years age were evaluated. Assessments included Motor Function Measure 32 (MFM32), myometry (knee flexors extensors, elbow extensors), goniometry extension), pulmonary function tests, quality-of-life...