Nervous System Diseases Commons^™

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Dissociating Statistically Determined Normal Cognitive Abilities And Mild Cognitive Impairment Subtypes With Dctclock., Emily F. Matusz, Catherine C. Price, Melissa Lamar, Rod Swenson, Rhoda Au, Sheina Emrani, Victor Wasserman, David J Libon, Louisa I. Thompson

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia.

METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning.

RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total …

Multiple Sclerosis And Neuromyelitis Optica Spectrum Disorder: Onset Following Acute Covid-19 Infection, A Case Series, Mirla Avila, Yuanyuan Tan, Roberto Hernandez, Hafsa Zuberi, Victor M Rivera

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: Acute COVID-19 infection has been associated with neurological involvement. We report a case series of newly diagnosed patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) developed in a short period of time after acute COVID-19 infection.

METHODS: New MS patients developing initial symptoms shortly after an acute COVID-19 infection were diagnosed based on the 2017 McDonald Criteria [Garcia-Ramos et al. in Cells, 2021]. The patients diagnosed with NMOSD met the 2015 International Panel criteria for the diagnosis of NMOSD (IPDN) [Thompson et al. in Lancet Neurol 17:162-173, 2018].

RESULTS FROM THE MS PATIENT GROUP: …

Demonstrating New-Onset Or Worsened Sudomotor Function Post-Covid-19 On Comparative Analysis Of Autonomic Function Pre-And Post-Sars-Cov-2 Infection, Aditi Varma-Doyle, Nicole R. Villemarette-Pittman, Paul Lelorier, John England

School of Medicine Faculty Publications

Background: Autonomic dysfunction including sudomotor abnormalities have been reported in association with SARS-CoV-2 infection. Objective: There are no previous studies that have compared autonomic function objectively in patients pre- and post- SARS-CoV-2 infection. We aimed to identify if SARS-CoV-2 virus is triggering and/or worsening dysautonomia by comparing autonomic function tests in a group of patients pre-and post-SARS-CoV-2 infection. Design/methods: Six participants were enrolled and divided into two groups. The first group of 4 participants reported worsened autonomic symptoms post-SARS-CoV-2 infection. These individuals had their first autonomic test prior to COVID-19 pandemic outbreak (July 2019–December 2019). Autonomic function testing was repeated …

Estimating Dementia Risk In An African American Population Using The Dctclock, Marissa Ciesla, Jeff Pobst, Joyce Gomes-Osman, Melissa Lamar, Lisa L Barnes, Russell Banks, Ali Jannati, David Libon, Rodney Swenson, Sean Tobyne, David Bates, John Showalter, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The prevalence of Alzheimer's disease (AD) and related dementias (ADRD) is increasing. African Americans are twice as likely to develop dementia than other ethnic populations. Traditional cognitive screening solutions lack the sensitivity to independently identify individuals at risk for cognitive decline. The DCTclock is a 3-min AI-enabled adaptation of the well-established clock drawing test. The DCTclock can estimate dementia risk for both general cognitive impairment and the presence of AD pathology. Here we performed a retrospective analysis to assess the performance of the DCTclock to estimate future conversion to ADRD in African American participants from the Rush Alzheimer's Disease Research …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Regional Fa Values And Loss Of Consciousness In Mild Traumatic Brain Injury, Alexander Asturias, Thomas Knoblauch, Alan Rodriguez, Cheryl Vanier, Caroline Le Tohic, Brandon Barrett, Michael Eisenberg, Rachelle Gibbert, Lennon Zimmerman, Shaunaq Parikh, Anh Nguyen, Sherwin Azad, Leo Germin, Enrico Fazzini, Travis Snyder

Far West Division GME Research Day 2023

No abstract provided.

A Case Of Thrombolytic Associated Ich In The Setting Of Infective Endocarditis, Priscilla Yan, Lama Al-Khoury

Far West Division GME Research Day 2023

No abstract provided.

Wernicke Encephalopathy: Interplay Between Magnesium And Thiamine, Richard Allen Gorman Ii, Mark Stine, Rafael Vaello, Patrick J. Stocker

West Florida Division GME Research Day 2023

No abstract provided.

Risk Factors For Depression Progression In Parkinson's Disease: A Retrospective Cohort Study, David Kosoy, James Cassuto, Gregory Kurgansky

East Florida Division GME Research Day 2023

Introduction: Depression is a common non-motor symptom in Parkinson's disease (PD) with a significant impact on quality of life and overall prognosis. Despite the availability of effective treatments, many PD patients with depression do not receive timely diagnosis and appropriate intervention. This study aimed to identify risk factors for depression progression in PD to inform clinical practice and future research.

Methods: We conducted a retrospective cohort study of PD patients using registry data from the Parkinson's Progression Markers Initiative (PPMI) dataset. The primary outcome was depression progression, defined as a 2-point or greater increase in the MDS-UPRDS depression score within …

Anti-Nmda Encephalitis In A Patient With Active Covid-19 Infection, Ali Abu-Alya, Janita Sidhu, Hamza Hansoti, Tyler Voss-Hamrick, Venkatachalam Veerappan, Ruhin Sidhu

Far West Division GME Research Day 2023

No abstract provided.

Microvascular Compression Causing Strokes From Subdural Hematoma Treated By Middle Meningeal Artery Embolization, Roy S. Escobar, Ali Abu-Alya, Vishnu Halthore, Julia Collins, Tanvir Khosla, Hamza Hansoti, Janite Sidhu, Venkatachalam Veerappan, Cyndi Tran

Far West Division GME Research Day 2023

No abstract provided.

Case Based Review On Headaches And Cerebral Venous Thromboembolism Post Covid-19 Infection, Aishwarya Raich, Tanvir Khosla, Vishnu Halthore, Ali Abu-Alya, Venkatachalam Veerappan

Far West Division GME Research Day 2023

No abstract provided.

Sudden Onset Ams, Focal Weakness, Fever And Aphasia Due To Intracranial Subdural Empyema In Left Temporo-Parietal Lobe, Lily Hyunjung Lim, Menachem M. Nagar, Pallavi Aneja

East Florida Division GME Research Day 2023

Intracranial subdural empyema (ISE) is a rare infection of brain, which occurs when pus is collectively located in the space between dura and arachnoid matter. In the past, its mortality was nearly 100%, if it was not treated appropriately within 24-48 hours. Thanks to improvement of diagnostic modalities and treatment, its mortality has dramatically decreased. Though, it can still cause a devastating consequence if it is not managed in a timely manner. The common etiology of ISE is different depending on the age group. In younger patients, it occurs frequently as a complication of infection in neighboring structures like sinusitis …

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Examining A Blood Biomarker Approach To Blood-Brain Barrier Disruption, Samantha Ford

Theses and Dissertations--Medical Sciences

Blood-brain barrier disruption has been identified to associate with the pathogenesis several neurological diseases such as dementia [1, 2], multiple sclerosis[3, 4], acute or chronic cerebral ischemia[5], brain trauma[5], meningitis[5], encephalitis[5], stroke[6], and seizures[7]. Being able to effectively identify blood-brain barrier disruption is limited in methodology. The current standard is using a cerebrospinal fluid (CSF) albumin to serum albumin index, which requires the use of a lumbar puncture. A novel method of identifying blood-brain barrier disruption utilizing blood biomarkers is proposed in this study. Participants in this study had previously collected blood and CSF samples, which were analyzed to compare …

Community Socioeconomic And Urban-Rural Differences In Emergency Medical Services Times For Suspected Stroke In North Carolina, Srihari V Chari, Eric R Cui, Haylie E Fehl, Antonio R Fernandez, Jane H Brice, Mehul D Patel

Faculty, Staff and Student Publications

OBJECTIVE: Our objectives were to describe time intervals of EMS encounters for suspected stroke patients in North Carolina (NC) and evaluate differences in EMS time intervals by community socioeconomic status (SES) and rurality.

METHODS: This cross-sectional study used statewide data on EMS encounters of suspected stroke in NC in 2019. Eligible patients were adults requiring EMS transport to a hospital following a 9-1-1 call for stroke-like symptoms. Incident street addresses were geocoded to census tracts and linked to American Community Survey SES data and to rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based …

Subcortical Functional Connectivity And Its Association With Walking Performance Following Deployment Related Mild Tbi, Mary R Newsome, Sarah L Martindale, Nicholas Davenport, Emily L Dennis, Marlene Diaz, Carrie Esopenko, Cooper Hodges, George R Jackson, Qisheng Liu, Kimbra Kenney, Andrew R Mayer, Jared A Rowland, Randall S Scheibel, Joel L Steinberg, Brian A Taylor, David F Tate, J Kent Werner, William C Walker, Elisabeth A Wilde

Faculty, Staff and Students Publications

INTRODUCTION: The relation between traumatic brain injury (TBI), its acute and chronic symptoms, and the potential for remote neurodegenerative disease is a priority for military research. Structural and functional connectivity (FC) of the basal ganglia, involved in motor tasks such as walking, are altered in some samples of Service Members and Veterans with TBI, but any behavioral implications are unclear and could further depend on the context in which the TBI occurred.

METHODS: In this study, FC from caudate and pallidum seeds was measured in Service Members and Veterans with a history of mild TBI that occurred during combat deployment, …

Seizures, Vitamin D Deficiency, And Severe Hypophosphatemia: The Unique Presentation Of A Sars-Cov-2 Case, Benson Yeh, Christopher Bell, Christopher Anderson, Mack Sheraton

Faculty, Staff and Student Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the species severe acute respiratory syndrome-related coronavirus (SARSr-CoV), which is related to the SARS-CoV-1 virus that caused the 2002-2004 SARS outbreak. SARS-CoV-2 causes coronavirus disease 2019 (COVID-19). It has been associated with electrolyte abnormalities. In this report, we discuss the case of a SARS-CoV-2-infected person presenting with recurrent seizure episodes resulting from hypophosphatemia. A 52-year-old male patient with questionable prior seizure history presented to the emergency department (ED) twice within eight days with recurring seizure episodes. While the physical examination at the first presentation was significant for …

How To Manage The Initiation Of Apomorphine Therapy Without Antiemetic Pretreatment: A Review Of The Literature, Stuart H. Isaacson, Richard B. Dewey, Rajesh Pahwa, Daniel E. Kremens

Department of Neurology Faculty Papers

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as …

Endovascular Repair Of Intercostal Patch Aneurysms In A Patient With Loyes-Dietz Syndrome, Guilherme B Lima, Laura Ocasio, Marina Dias-Neto, Emanuel R Tenorio, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

No abstract provided.

Massive Macroglossia, A Rare Side Effect Of Covid-19: Clinical, Histologic, And Genomic Findings In Covid-19-Positive Versus Covid-19-Negative Patients, Victoria A Mañón, David Chubb, Laura S Farach, Rachid Karam, Mary C Farach-Carson, Nadarajah Vigneswaran, Karan Saluja, Simon Young, Mark Wong, James C Melville

Faculty, Staff and Student Publications

PURPOSE: The primary purpose of this study is to identify if there is an underlying genetic predisposition for COVID-related macroglossia and if this susceptibility is higher among individuals of African heritage. Secondary objectives include determining if genetic testing of COVID-infected patients who are intubated and prone could identify patients with higher susceptibility to the development of macroglossia.

METHODS: A retrospective chart review was completed for each patient, and prospectively, genetic and histopathologic analyses were completed. Whole-exome sequencing was completed on two patients; immunohistochemistry was completed on the COVID-positive tissue samples.

RESULTS: Histopathology of the COVID-positive patient revealed significant peri-lymphocytic infiltrate, …

Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges In Patients With Focal Epilepsy, Shennan A. Weiss, Laurent Sheybani, Nitish Seenarine, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel Jr., Michael R. Sperling, Yuval Nir, Richard J. Staba

Department of Neurology Faculty Papers

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …

Living With Brain Cancer: From Researcher To Patient, Stephen P. Chelko, Daniel L. Fay Ph.D.

Patient Experience Journal

As an academic researcher, my work-life revolves around testing the efficaciousness of pharmaceutical drugs on the prevention of cardiac dysfunction, arrhythmias, and sudden cardiac death in animal models of heart disease. I never thought I would go from someone studying a life-threatening disease to a patient living with one in twenty-four hours. Yet, that transformation occurred October 8, 2019. I was just appointed to Assistant Professor at Johns Hopkins University School of Medicine (JHUSOM), yet after sitting for my professional headshot I had a grand mal seizure. I cannot recall this event, but I bit the tip of my tongue …

What Do We Know So Far About Ofatumumab For Relapsing Multiple Sclerosis? A Meta-Analytical Study, Hafiza Munazza Taj, Maryam Talib, Sania Siddiqa, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Ofatumumab is a monoclonal antibody that reduces the level of B cells that alter the progression of relapsing multiple sclerosis. Originally approved by the Food and Drug Administration (FDA) in August 2020, this meta-analysis determines the outcomes of four randomized controlled trials (RCTs) for endline outcomes of Gadolinium-enhancing T1 lesions on MRI scans reported as Cohen's d and relapse rate reported as risk ratio. All four RCTs reported favorable findings of gadolinium-enhancing T1 lesions (Cohen's d = -0.44, p < 0.00001). The relapse rate was reduced by 46% post ofatumumab administration (RR = 0.54, p < 0.00001). With 14 ongoing trials in this area, more data is required to consolidate our findings.

Spontaneous Pneumothorax: A Rare Complication Of Neurofibromatosis Type 1 Associated Diffuse Lung Disease, Emma I. Sherfinski, Mark H. Cooper Md, Phd

Marshall Journal of Medicine

The visually striking neurocutaneous findings of neurofibromatosis type 1 (NF1) are well recognized and have been well documented throughout scientific literature. While not uncommon, the pulmonary manifestations of NF1 are unknown to many physicians. Complications of NF1 associated diffuse lung disease (NF-DLD) include pulmonary hypertension, pulmonary artery stenosis, subpleural cysts, and spontaneous pneumothorax. We present a case of a 34-year-old male with NF-DLD found incidentally in adolescence with previous apical bleb repair, presenting nearly twenty years later with spontaneous pneumothorax. In NF1 patients with pulmonary complaints, NF-DLD should be assessed with computed tomography (CT) and physicians should be familiar with …

Alzheimer's Disease, Dylan L. Weber

Student Publications

An overview of the background, etiology, pathophysiology, clinical features, diagnosis, treatment and prevention of Alzheimer's disease.

Heterozygous Variants In Myh10 Associated With Neurodevelopmental Disorders And Congenital Anomalies With Evidence For Primary Cilia-Dependent Defects In Hedgehog Signaling, Alexander M Holtz, Rachel Vancoillie, Elizabeth A Vansickle, Deanna Alexis Carere, Kara Withrow, Erin Torti, Jane Juusola, Francisca Millan, Richard Person, Maria J Guillen Sacoto, Yue Si, Ingrid M Wentzensen, Jada Pugh, Georgia Vasileiou, Melissa Rieger, André Reis, Emanuela Argilli, Elliott H Sherr, Kimberly A Aldinger, William B Dobyns, Theresa Brunet, Julia Hoefele, Matias Wagner, Benjamin Haber, Urania Kotzaeridou, Boris Keren, Delphine Heron, Cyril Mignot, Solveig Heide, Thomas Courtin, Julien Buratti, Serini Murugasen, Kirsten A Donald, Emily O'Heir, Shade Moody, Katherine H Kim, Barbara K Burton, Grace Yoon, Miguel Del Campo, Diane Masser-Frye, Mariya Kozenko, Christina Parkinson, Susan L Sell, Patricia L Gordon, Jeremy W Prokop, Amel Karaa, Caleb Bupp, Benjamin A Raby

Faculty, Staff and Student Publications

PURPOSE: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.

METHODS: An international collaboration identified the patient cohort. CAS9-mediated knockout cell models were used to explore the mechanism of disease pathogenesis.

RESULTS: We identified a cohort of 16 individuals with heterozygous MYH10 variants presenting with a …