Medical Specialties Commons^™

Sox7 Deficiency Causes Ventricular Septal Defects Through Its Effects On Endocardial-To-Mesenchymal Transition And The Expression Of Wnt4 And Bmp2, Andrés Hernández-García, Katherine E Pendleton, Sangbae Kim, Yumei Li, Bum J Kim, Hitisha P Zaveri, Valerie K Jordan, Aliska M Berry, M Cecilia Ljungberg, Rui Chen, Rainer B Lanz, Daryl A Scott

Faculty, Staff and Students Publications

SOX7 is a transcription factor-encoding gene located in a region on chromosome 8p23.1 that is recurrently deleted in individuals with ventricular septal defects (VSDs). We have previously shown that Sox7-/- embryos die of heart failure around E11.5. Here, we demonstrate that these embryos have hypocellular endocardial cushions with severely reduced numbers of mesenchymal cells. Ablation of Sox7 in the endocardium also resulted in hypocellular endocardial cushions, and we observed VSDs in rare E15.5 Sox7flox/-;Tie2-Cre and Sox7flox/flox;Tie2-Cre embryos that survived to E15.5. In atrioventricular explant studies, we showed that SOX7 deficiency leads to a severe reduction in endocardial-to-mesenchymal transition (EndMT). RNA-seq …

Induction Of Astrocytic Slc22a3 Regulates Sensory Processing Through Histone Serotonylation, Debosmita Sardar, Yi-Ting Cheng, Junsung Woo, Dong-Joo Choi, Zhung-Fu Lee, Wookbong Kwon, Hsiao-Chi Chen, Brittney Lozzi, Alexis Cervantes, Kavitha Rajendran, Teng-Wei Huang, Antrix Jain, Benjamin R Arenkiel, Ian Maze, Benjamin Deneen

Faculty, Staff and Students Publications

Neuronal activity drives alterations in gene expression within neurons, yet how it directs transcriptional and epigenomic changes in neighboring astrocytes in functioning circuits is unknown. We found that neuronal activity induces widespread transcriptional upregulation and downregulation in astrocytes, highlighted by the identification of a neuromodulator transporter Slc22a3 as an activity-inducible astrocyte gene regulating sensory processing in the olfactory bulb. Loss of astrocytic Slc22a3 reduced serotonin (5HT) levels in astrocytes, leading to alterations in histone serotonylation. Inhibition of histone serotonylation in astrocytes reduced expression of GABA biosynthetic genes and GABA release, culminating in olfactory deficits. Our study revealed that neuronal activity …

Aging Fly Cell Atlas Identifies Exhaustive Aging Features At Cellular Resolution, Tzu-Chiao Lu, Maria Brbić, Ye-Jin Park, Tyler Jackson, Jiaye Chen, Sai Saroja Kolluru, Yanyan Qi, Nadja Sandra Katheder, Xiaoyu Tracy Cai, Seungjae Lee, Yen-Chung Chen, Niccole Auld, Chung-Yi Liang, Sophia H Ding, Doug Welsch, Samuel D'Souza, Angela Oliveira Pisco, Robert C Jones, Jure Leskovec, Eric C Lai, Hugo J Bellen, Liqun Luo, Heinrich Jasper, Stephen R Quake, Hongjie Li

Duncan NRI Faculty and Staff Publications

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We characterize 163 distinct cell types and perform an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further develop aging clock models to predict the fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find unique cell type-specific aging patterns. This atlas provides a …

Poly(A)-Binding Protein Is An Ataxin-2 Chaperone That Regulates Biomolecular Condensates, Steven Boeynaems, Yanniv Dorone, Yanrong Zhuang, Victoria Shabardina, Guozhong Huang, Anca Marian, Garam Kim, Anushka Sanyal, Nesli-Ece Şen, Daniel Griffith, Roberto Docampo, Keren Lasker, Iñaki Ruiz-Trillo, Georg Auburger, Alex S Holehouse, Edor Kabashi, Yi Lin, Aaron D Gitler

Duncan NRI Faculty and Staff Publications

Biomolecular condensation underlies the biogenesis of an expanding array of membraneless assemblies, including stress granules (SGs) which form under a variety of cellular stresses. Advances have been made in understanding the molecular grammar of a few scaffold proteins that make up these phases, but how the partitioning of hundreds of SG proteins is regulated remains largely unresolved. While investigating the rules that govern the condensation of ataxin-2, a SG protein implicated in neurodegenerative disease, we unexpectedly identified a short 14aa sequence that acts as a condensation switch and is conserved across the eukaryote lineage. We identify poly(A)-binding proteins as unconventional …

A Novel Comorbidity Score For Older Adults With Non-Hodgkin Lymphoma: The 3-Factor Risk Estimate Scale, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Alessandra Ferrajoli, Alexey V Danilov, Sharon H Giordano

Faculty, Staff and Student Publications

For patients with non-Hodgkin lymphoma (NHL), formal comorbidity assessment is recommended but is rarely conducted in routine practice. A simple, validated measure of comorbidities that standardizes their assessment could improve adherence to guidelines. We previously constructed the 3-factor risk estimate scale (TRES) among patients with chronic lymphocytic leukemia (CLL). Here, we investigated TRES in multiple NHL subtypes. In the surveillance, epidemiology, and end results-Medicare database, patients with NHL diagnosed from 2008 to 2017 were included. Upper gastrointestinal, endocrine, and vascular comorbidities were identified using ICD-9/ICD-10 codes to assign TRES scores. Patient characteristic distributions were compared using χ2 or t test. …

Biological Mechanism Of Sex Difference In Stroke Manifestation And Outcomes, Wi-Sun Ryu, Jinyong Chung, Dawid Schellingerhout, Sang-Wuk Jeong, Hang-Rai Kim, Jung E Park, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Kyungbok Lee, Tai Hwan Park, Sang-Soon Park, Jong-Moo Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Man Seok Park, Kang-Ho Choi, Juneyoung Lee, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location.

METHODS: This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 >days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods …

Neurocognitive Dysfunction With Neuronal Injury In People With Hiv On Long-Duration Antiretroviral Therapy, Cynthia Mcmahan, Devon K Dietrich, Elizabeth F Horne, Erin Kelly, Katrina Geannopoulos, Peter Selim Siyahhan Julnes, Lillian Ham, Ulisses Santamaria, Chuen-Yen Lau, Tianxia Wu, Hsing-Chuan Hsieh, Anuradha Ganesan, Catherine Berjohn, Suad Kapetanovic, Daniel S Reich, Govind Nair, Joseph Snow, Brian K Agan, Avindra Nath, Bryan R Smith

Staff and Researcher Publications

Background and objectives: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses.

Methods: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was …

Effects Of Spaceflight On The Eeg Alpha Power And Functional Connectivity, Sandra Pusil, Jonathan Zegarra-Valdivia, Pablo Cuesta, Christopher Laohathai, Ana Maria Cebolla, Jens Haueisen, Patrique Fiedler, Michael Funke, Fernando Maestú, Guy Cheron

Faculty, Staff and Student Publications

Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN's alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.

A Rare Case Of Combined Immunodeficiency Syndrome With Otomastoiditis, Parotitis & Facial Nerve Palsy, Parth Garg, Amulya T M, Prakash B.G., Sandhya D

Digital Journal of Clinical Medicine

This article presents a case study of a 4-month-old female baby with combined immunodeficiency syndrome complicated by bilateral otomastoiditis, right-sided parotitis, and facial nerve palsy. The patient presented with symptoms of fever, cold, earache, and ear discharge. Clinical examination revealed redness and swelling in the post-auricular region, along with bloody discharge from the right ear. Further investigations, including blood tests, culture sensitivity, ultrasound scans, and imaging studies, confirmed the diagnosis. The patient was treated with appropriate antibiotics, antifungals, and supportive care. The article discusses the challenges in diagnosing and managing primary immunodeficiency diseases (PIDs), emphasising the importance of early recognition …

Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome) – A Case Report, Rudrani Mukherjee, Bhanukumar M

Digital Journal of Clinical Medicine

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg Strauss syndrome, is a rare small vessel vasculitis characterized by asthma, eosinophilia, and systemic involvement. This case report presents a 51-year-old man with a history of asthma, who presented with neurological symptoms including blurring of vision, bilateral ptosis, and altered sensorium. The patient had a previous history of cervical and lumbar spine surgeries for symptoms attributed to spondylosis. Further examination revealed hyperpigmented lesions on the limbs, wasting of small muscles, and foot drop.

Investigations showed eosinophilia and thrombocytosis on blood analysis, with bone marrow aspiration revealing eosinophilic and megakaryocytic hyperplasia. The …

Chronic Basal Forebrain Activation Improves Spatial Memory, Boosts Neurotrophin Receptor Expression, And Lowers Bace1 And Aβ42 Levels In The Cerebral Cortex In Mice, Jacob Kumro, Ashutosh Tripathi, Yun Lei, Jeremy Sword, Patrick Callahan, Alvin Terry, Xin-Yun Lu, Sergei A Kirov, Anilkumar Pillai, David T Blake

Faculty, Staff and Student Publications

The etiology of Alzheimer’s dementia has been hypothesized in terms of basal forebrain cholinergic decline, and in terms of reflecting beta-amyloid neuropathology. To study these different biological elements, we activated the basal forebrain in 5xFAD Alzheimer’s model mice and littermates. Mice received 5 months of 1 h per day intermittent stimulation of the basal forebrain, which includes cholinergic projections to the cortical mantle. Then, mice were behaviorally tested followed by tissue analysis. The 5xFAD mice performed worse in water-maze testing than littermates. Stimulated groups learned the water maze better than unstimulated groups. Stimulated groups had 2–3-fold increases in frontal cortex …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer's Disease: Research Outline And Call For Collaboration., Richard Lathe, Nikki M Schultek, Brian J. Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi

PCOM Scholarly Works

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

Journal Club: Glymphatic System In Neurodegenerative Diseases, Ronald G. Lott Iii, Xavier Zonna, Samuel Wlasowicz

Advances in Clinical Medical Research and Healthcare Delivery

Neurodegenerative diseases such as Alzheimer's Disease impact a multitude of individuals worldwide. The neural Glymphatic system is a relatively newly discovered cellular transport pathway within the brain that has been implicated in neurodegenerative diseases. This article serves to provide a journal club review of current literature on the Glymphatic system to raise awareness of this system and its potential for future treatment and prevention of neurodegenerative conditions.

Intravenous Thrombolytic Therapies In The Management Of Unknown Onset And Wakeup Strokes: A Scoping Review, Saima Nazish

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT Background: The efficacy and safety of intravenous recombinant tissue plasminogen activator (IV rt-PA) for the management of unknown time onset stroke (UTOS) and wake-up stroke (WUS) are in a debate. Objective:The objective of this review is to discuss the UTOS and its management with intravenous thrombolytic therapies. Data Sources: Databases searched included PubMed and Cochrane electronic databases and manual search. Study Selection and Data Extraction: 45 articles of potential relevance were selected. Results: 14 relevant papers were included. Most of studies including recent trials using Magnetic resonance imaging diffusion-weighted imaging fluid-attenuated inversion recovery (MRIDWI FLAIR) mismatch or Computed tomography …

Fibromyalgia: The Misunderstood Victim, Wajid Jawaid

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Frequency Of Depression Among Patients With Parkinson Disease, Mohammad Lateef, Wasim Ikram Alvi, Abdul Malik, Neelum Jamal, Muhammad Umair, Muhammad Athar Khan

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Parkinson's disease is a degenerative neurological condition that affects a large number of individuals worldwide. One of the common non-motor symptoms associated with this disease is depression, which can pose challenges for both patients and their caregivers. The main objective of this research was to determine the frequency of depression among patients with Parkinson disease.

Methods:This was a cross-sectional study that was conducted in Karachi, Pakistan, between March 26, 2022, and September 30, 2022. Male and female patients diagnosed with Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria, who were …

Mandatory Child Neurology Training For Adult Neurology Residents In Pakistan, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

National Guidelines For The Treatment Of Common Headaches Disorders In Pakistan, Abdul Malik, Sabrina Khan, Mohammad Wasay, Aziz Sonawalla, Samaira Younis, Faisal Mohammad Amin

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Association Of Hyperuricemia With Ischemic Stroke In Adult Population, Ijaz Ali, Zaid Waqar, Bushra Khalid, Maryam Naseem, Soban Khan, Sajid Ali, Muhammad Tariq, Muhammad Adil, Hira Badar Abbasi, Mazhar Badshah

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Stroke is the second most prevalent cause of dementia, the third biggest cause of mortality, and the top cause of disability globally. Hyperuricemia is frequently seen in patients with vascular risk factors. The objective of this study was to determine the association of hyperuricemia with ischemic stroke in adult patients presenting to neurology department of a tertiary care hospital.

Methods:This was a case-control study of 200 patients, 100 patients with stroke and 100 unmatched controls were accessed for vascular risk factors and hyperuricemia. The setting was Pakistan Institute of Medical Sciences, Islamabad and study duration was …

Neurobehavioral And Biochemical Effects Of Choline Chloride Administration In Rats, Lubna Anis, Irfan Sajid, Shoaib Ahmad, Saida Haider

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective:

Choline is an essential nutrient related to vitamin B complex activity. It can be received through different food sources. It is an important component of acetylcholine which is involved in different brain functions. The present study is designed to assess the behavioral effects of choline chloride in animal models.

Methods:This case-control study was performed in the Department of Biochemistry, Federal Urdu University, Karachi for eight months from May 2022 to December 2022. Twenty-four adult male albino Wister rats were divided into four groups, one control and three test groups. Choline chloride dissolved in saline was given …

Chronic Hepatitis B, C, And Stroke; Association And Pathophysiology, Hamza Imran, Adnan Yousuf, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objectives:

Hepatitis infection may raise the incidence of stroke and other cerebrovascular abnormalities, according to several studies. However, its association is controversial. This review looked to compile the most recent research on the relationship between HBV and HCV, atherosclerosis, and stroke.

Methods:This article reviews the literature on the connection between hepatitis B and C viruses with stroke and atherosclerosis. The search included articles from PubMed, PakMediNet, and Google Scholar, as well as a Medline search using specific keywords and MeSH terms. A total of 2655 articles were identified. Out of these 2655 articles we identified 134 articles …

Lack Of Stroke Care Centers In Sindh, Adnan Malik, Rahul Agia

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Terson Syndrome In A Patient With Unrepaired Tetralogy Of Fallot, Amina Saddiqa, Zaid Waqar, Maryam Khalil, Muhammad Anas, Zeeshan Munawar, Ifrah Ayaz, Zakir Jan, Haris Majid

Pakistan Journal of Neurological Sciences (PJNS)

Tetralogy of Fallot is the most commonly seen cyanotic congenital heart disease. It includes four cardinal features: right ventricular outflow tract obstruction, misaligned ventricular septal defect, overriding aorta, and concentric right ventricular hypertrophy. Intracranial pathologies such as brain abscesses, cerebrovascular accidents, and intracranial haemorrhage all have been reported with Tetralogy of Fallot. Here we present a case who had subarachnoid haemorrhage with vitreous haemorrhage in Tetralogy of Fallot.

Clinical Presentation, Evaluation, And Management Of Patients With Myasthenia Gravis At A Tertiary Care Center In Pakistan, Aziz Sonawalla, Shafaq Saleem, Salim Allana, Rabia Qaiser, Rohma Shamsi

Pakistan Journal of Neurological Sciences (PJNS)

Background and objectives:

Little is known about the clinical profile and outcome of myasthenia gravis in Pakistan. The objective of this study is to review the clinical characteristics of patients with myasthenia gravis in Pakistan, and the outcome of investigations and treatment.

Methods: The study comprised a retrospective review of charts of patients diagnosed with myasthenia gravis at Aga Khan University Hospital in Karachi, Pakistan, over a period of 16 years from 1987 to 2003. The following features were reviewed: (i) clinical presentation, (ii) investigations especially nerve conduction studies, acetylcholine receptor antibodies, and imaging studies of the thorax, (iii) treatments …

Cerebellar Manifestation Secondary To Rectal Neoplasia, Soban Khan, Zaid Waqar, Maryam Khalil, Bushra Khalid, Sajid Ali, Ijaz Ali, Muhammad Tariq, Muhammad Adil

Pakistan Journal of Neurological Sciences (PJNS)

The condition known as paraneoplastic cerebellar degeneration (PCD) is among the most disabling examples of a cancer's remote effects. Serology for paraneoplastic antibodies, clinical suspicion, and a targeted search for malignancy all play a role in the diagnosis. Tests for neuronal autoantibodies aid in diagnosis and point the way for the search for malignancy. Unfortunately, even with an early diagnosis, existing therapeutic approaches only have little success. Here we present the case of a young male who developed cerebellar syndrome secondary to rectal neoplasia.

Frequency Of Hyperlipedemia In Patients Coming With Ischemic Stroke In Tertiary Care Hospital Karachi, Bushra Ammad, Abdul Malik, Rabia Sana Muhammad, Maryam Javed, Hina Imtiaz

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective:

Stroke is the second leading cause of death and the third leading cause of disability. This study was designed to determine the frequency of hyperlipidemia in patients with ischemic stroke visiting at a tertiary care hospital in Karachi.

Methods:This was a descriptive cross-sectional study and was done in Department of Medicine, LCMD/ Dar-ul-Sehat Hospital Karachi, Pakistan. A total of 184 patients were studied during the study period of six months and all the consecutive patients were recruited who presented with acute stroke in the department of medicine from the duration April 1st 2022 to September 30th, …

Interleukin-1 Signaling And Alcohol-Induced Cortical Dysfunction, Florence Varodayan, Amanda Pahng, Tony Davis, T. Nadav, I. Polis, C.C. Cates-Gatto, Michal Bajo, Michael D. Burkart, Scott Edwards, Amanda J. Roberts, Marisa Roberto

School of Medicine Faculty Publications

Alcoholism and Stress: A Framework for Future Treatment Strategies; Volterra, Italy; May 16-19, 2023

Actigraphic Correlates Of Neuropsychiatric Symptoms In Adults With Focal Epilepsy, Mark A Abboud, Jessica L Kamen, John S Bass, Lu Lin, Jay R Gavvala, Sindhu Rao, Stephen F Smagula, Vaishnav Krishnan

Faculty, Staff and Student Publications

Objectives:

Disability in patients with epilepsy (PWEs) is multifactorial: beyond seizure frequency/severity, PWEs are prone to a range of neuropsychiatric, cognitive, and somatic comorbidities that significantly affect quality of life. Here, we explored how variations in seizure severity and the burden of self-reported somatic/neuropsychiatric symptoms correlate with disruptions to 24 h activity patterns (rest-activity rhythms [RARs]), determined through wrist accelerometry/actigraphy.

Methods:

Multiday wrist-actigraphy recordings were obtained from 59 adult patients with focal epilepsy (44% male, ages 18–72), who contemporaneously responded to validated psychometric instruments to measure anxiety, depression, sleepiness, and somatic symptoms. We conducted a similar in silico psychometric-actigraphic correlation …

Mortality In Asia Impairment Scale Grade A To D Patients With Odontoid Fracture And Magnetic Resonance Imaging Evidence Of Spinal Cord Injury, Bizhan Aarabi, Christopher J Neal, David S. Hersh, James S. Harrop, Michael G. Fehlings, Elizabeth G. Toups, James D. Guest, Beatrice Ugiliweneza, Noori Akhtar-Danesh, Shekar N. Kurpad, Robert G. Grossman

Department of Neurosurgery Faculty Papers

Odontoid fractures are common, often presenting in the elderly after a fall and infrequently associated with traumatic spinal cord injury (tSCI). The goal of this study was to analyze predictors of mortality and neurological outcome when odontoid fractures were associated with signal change on magnetic resonance imaging (MRI) at admission. Over an 18-year period (2001-2019), 33 patients with odontoid fractures and documented tSCI on MRI were identified. Mean age was 65.3 years (standard deviation [SD] = 17.2), and 21 patients were male. The mechanism of injury was falls in 25 patients, motor vehicle accidents in 5, and other causes in …

De Novo Variants In Mrtfb Have Gain-Of-Function Activity In Drosophila And Are Associated With A Novel Neurodevelopmental Phenotype With Dysmorphic Features, Jonathan C Andrews, Jung-Wan Mok, Oguz Kanca, Sharayu Jangam, Cynthia Tifft, Ellen F Macnamara, Bianca E Russell, Lee-Kai Wang, Undiagnosed Diseases Network, Stanley F Nelson, Hugo J Bellen, Shinya Yamamoto, May Christine V Malicdan, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Purpose: Myocardin-related transcription factor B (MRTFB) is an important transcriptional regulator, which promotes the activity of an estimated 300 genes but is not known to underlie a Mendelian disorder.

Methods: Probands were identified through the efforts of the Undiagnosed Disease Network. Because the MRTFB protein is highly conserved between vertebrate and invertebrate model organisms, we generated a humanized Drosophila model expressing the human MRTFB protein in the same spatial and temporal pattern as the fly gene. Actin binding assays were used to validate the effect of the variants on MRTFB.

Results: Here, we report 2 pediatric probands with de novo …