A5054611483- Genetic Syndromes and Imprinting
- Lysosomal Storage Disorders Research
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Genomic variations and chromosomal abnormalities
- Prenatal Screening and Diagnostics
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Glycogen Storage Diseases and Myoclonus
- Neurological diseases and metabolism
- Autophagy in Disease and Therapy
- Muscle Physiology and Disorders
- Craniofacial Disorders and Treatments
- Ubiquitin and proteasome pathways
- Congenital heart defects research
- Fetal and Pediatric Neurological Disorders
- Bone health and treatments
- Neurogenetic and Muscular Disorders Research
- Metabolism and Genetic Disorders
- Tumors and Oncological Cases
- Folate and B Vitamins Research
- Congenital Ear and Nasal Anomalies
University of California, Irvine Medical Center
2013-2025
University of California, Irvine
2016-2025
Children's Hospital of Orange County
2013-2025
LAC+USC Medical Center
2023
University of California, San Diego
2023
University of Southern California
2023
Tripler Army Medical Center
2023
Cedars-Sinai Medical Center
2023
Illinois College
2023
UC Irvine Health
2018-2021
Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3–q31, and caused by mutations in PTC, the human homologue of Drosophila patched gene, comprises multiple carcinomas, keratocysts jaw, palmar/plantar pits, spine rib anomalies calcification falx cerebri. We reviewed findings on 105 affected individuals examined at NIH since 1985. The data included 48 males 57 females ranging age from 4 months 87 years. Eighty percent whites (71/90) 38%...
VCP (VCP/p97) is a ubiquitously expressed member of the AAA+-ATPase family chaperone-like proteins that regulates numerous cellular processes including chromatin decondensation, homotypic membrane fusion, and ubiquitin-dependent protein degradation by proteasome. Mutations in cause multisystem degenerative disease consisting inclusion myopathy, Paget’s bone, frontotemporal dementia (IBMPFD). Here we show essential for autophagosome maturation. We generated cells stably expressing dual-tagged...
Abstract Prader–Willi syndrome (PWS) is a complex neurobehavioral condition which has been classically described as having two nutritional stages: poor feeding, frequently with failure to thrive (FTT) in infancy (Stage 1), followed by hyperphagia leading obesity later childhood 2). We have longitudinally the feeding behaviors of individuals PWS and found much more gradual progression phases than traditional stages literature. Therefore, this study characterizes growth, metabolic, laboratory...
Frontotemporal dementia with inclusion body myopathy and Paget disease of bone is a rare, autosomal-dominant disorder caused by mutations in the gene valosin-containing protein (VCP). The CNS pathology characterized novel pattern ubiquitin distinct from sporadic familial frontotemporal lobar degeneration ubiquitin-positive inclusions (FTLD-U) without VCP mutations. TAR DNA binding 43 (TDP-43) was recently identified as major FTLD-U. To determine whether associated accumulation TDP-43, we...
TAR DNA binding protein-43 (TDP-43) is found in ubiquitinated inclusions (UBIs) some frontotemporal dementias (FTD-U). One form of FTD-U, due to mutations the valosin containing protein (VCP) gene, occurs with an inclusion body myopathy (IBMPFD). Since IBMPFD brain has TDP-43 UBIs, we looked for muscle. In normal muscle, present nuclei. additionally as large within UBIs muscle cytoplasm. were also 78% sporadic myositis (sIBM) muscles. and sIBM migrated additional band on immunoblot similar...
Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in disease remains unclear. Here, we used single-cell transcriptomics determine molecular attributes dystrophic and healthy macrophages. We identified six clusters unexpectedly found that none corresponded traditional definitions M1 or M2 Rather, predominant macrophage signature was characterized by high expression fibrotic factors, galectin-3 (gal-3) osteopontin...
Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant muscular in which no mutation of pathogenic gene(s) has been identified. Instead, the disease is, most cases, genetically linked to a contraction number 3.3 kb D4Z4 repeats on chromosome 4q. How 4qter causes not understood. In addition, smaller group FSHD cases are associated with repeat (termed "phenotypic" FSHD), and their etiology remains undefined. We carried out chromatin immunoprecipitation analysis using D4Z4-specific PCR...
Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, member AAA-ATPase gene superfamily. The neuropathology associated sporadic FTD heterogeneous includes tauopathies frontotemporal lobar degeneration ubiquitin-positive inclusions (FTLD-U). However, there limited information on IBMPFD. We performed detailed, systematic analysis neuropathologic...
Mutations in the valosin-containing protein (VCP) gene on chromosome 9p13-p12 recently have been shown to cause autosomal dominant inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. Here, we report central nervous system autopsy findings a 55-year-old German patient dementia who harbors heterozygous R155C missense mutation residing N-terminal CDC48 domain VCP, which is involved ubiquitin binding. We demonstrate that mutant VCP causes novel type...
Abstract Inclusion body myopathy with Paget disease of the bone (PDB) and/or frontotemporal dementia (IBMPFD, OMIM 167320), is a progressive autosomal dominant disorder caused by mutations in Valousin‐containing protein (VCP, p97 or CDC48) gene. IBMPFD can be difficult to diagnose. We assembled data on large set families illustrate number and type misdiagnoses that occurred. Clinical analysis 49 affected individuals nine indicated 42 (87%) had muscle disease. The majority were erroneously...
Mutations in the valosin-containing protein (VCP, p97) gene on chromosome 9p13-p12 cause a late-onset form of autosomal dominant inclusion body myopathy associated with Paget disease bone and frontotemporal dementia (IBMPFD). We report pathological consequences three heterozygous VCP (R93C, R155H, R155C) mutations human striated muscle. IBMPFD skeletal muscle pathology is characterized by degenerative changes filamentous VCP- ubiquitin-positive cytoplasmic nuclear aggregates. Furthermore,...
Background Prader-Willi syndrome (PWS) is due to errors in genomic imprinting. PWS recognised as the most common known genetic cause of life-threatening obesity. This report summarises frequency and further characterises molecular classes maternal age effects. Methods High-resolution microarrays, comprehensive chromosome 15 genotyping methylation-specific multiplex ligation probe amplification were used describe characterise disomy (UPD15) considering age. Results We summarised data from 510...
Prader–Willi syndrome (PWS) is a rare, complex multisystem genetic disorder which includes hypothalamic dysfunction, hyperphagia, cognitive and behavioral problems, increased anxiety, compulsive behaviors. Individuals with PWS have deficit of oxytocin producing neurons in the paraventricular nucleus hypothalamus. Oxytocin plays role regulation feeding behaviors, social interactions, emotional reactivity, are all issues that significantly affect quality life for individuals this syndrome. We...