William A. Gahl
A5082442398- Biomedical Research and Pathophysiology
- melanin and skin pigmentation
- Neonatal Health and Biochemistry
- Genomics and Rare Diseases
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Genetic and Kidney Cyst Diseases
- Glycosylation and Glycoproteins Research
- RNA regulation and disease
- Biochemical Analysis and Sensing Techniques
- Lysosomal Storage Disorders Research
- Genomic variations and chromosomal abnormalities
- Inflammatory Myopathies and Dermatomyositis
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Neurogenetic and Muscular Disorders Research
- Histiocytic Disorders and Treatments
- RNA Research and Splicing
- Autoimmune and Inflammatory Disorders Research
- Cell Adhesion Molecules Research
- Folate and B Vitamins Research
- Erythrocyte Function and Pathophysiology
- Methemoglobinemia and Tumor Lysis Syndrome
National Human Genome Research Institute
2016-2025
National Institutes of Health
2016-2025
Office of the Director
2007-2025
Office of the Director
2015-2024
NIH Common Fund
2013-2023
Rady Children's Hospital-San Diego
2023
University of Wisconsin–Madison
1976-2022
University of California System
2022
Office of Extramural Research
2022
Foundation for Ichthyosis and Related Skin Types
2013-2022
Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated autoinflammatory disease, may define new disorders.We analyzed peripheral-blood exome sequence data independent of phenotype and inheritance pattern to identify deleterious mutations genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, transcriptome cytokine profiling were performed. CRISPR-Cas9-edited zebrafish...
Hutchinson–Gilford progeria syndrome is a rare, sporadic, autosomal dominant that involves premature aging, generally leading to death at approximately 13 years of age due myocardial infarction or stroke. The genetic basis most cases this change from glycine GGC GGT in codon 608 the lamin A (LMNA) gene, which activates cryptic splice donor site produce abnormal A; disrupts nuclear membrane and alters transcription.
Alkaptonuria, caused by mutations in the HGO gene and a deficiency of homogentisate 1,2-dioxygenase, results an accumulation homogentisic acid (HGA), ochronosis, destruction connective tissue. There is no effective therapy for this disorder, although nitisinone inhibits enzyme that produces HGA. We performed study to delineate natural history alkaptonuria.
Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, a renal salt-losing tubulopathy normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call EAST syndrome (the presence epilepsy, tubulopathy).
Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans (non-LCH), respectively. The discovery BRAF(V600E) mutations approximately 50% these patients provided the first molecular therapeutic target histiocytosis. However, recurrent driving majority with BRAF(V600E)-wild-type non-LCH unknown, cooperating non-MAP kinase pathways undefined for...
Arterial calcifications are associated with increased cardiovascular risk, but the genetic basis of this association is unclear.
Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply multidisciplinary model in the evaluation of most challenging cases and identify biologic characteristics newly discovered diseases. UDN, which is funded by National Institutes Health, formed 2014 as network seven clinical sites, two sequencing cores, coordinating center. Later, central biorepository, metabolomics core, organisms screening center were added.
PurposeThis report describes the National Institutes of Health Undiagnosed Diseases Program, details Program’s application genomic technology to establish diagnoses, and success rate during its first 2 years.MethodsEach accepted study participant was extensively phenotyped. A subset participants selected family members (29 patients 78 unaffected members) subjected an integrated set analyses including high-density single-nucleotide polymorphism arrays whole exome or genome analysis.ResultsOf...
Objective Early-onset epileptic encephalopathies have been associated with de novo mutations of numerous ion channel genes. We employed techniques modern translational medicine to identify a disease-causing mutation, analyze its altered behavior, and screen for therapeutic compounds treat the proband. Methods Three tools were utilized: (1) high-throughput sequencing technology novel mutation; (2) in vitro expression electrophysiology assays confirm variant protein's dysfunction; (3)...
Erdheim-Chester Disease (ECD) is a rare, potentially fatal, multi-organ myeloid neoplasm occurring mainly in adults. The diagnosis established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a-, frequently S100-. purpose of this report to describe the clinical molecular variability ECD. Sixty consecutive patients (45 males, 15 females) were prospectively evaluated at NIH Clinical Center between 2011 2015. Comprehensive imaging...
Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic luminal residues the TLR chaperone protein UNC93B1, which identified both negative positive regulatory regions affecting TLR3, TLR7, TLR9 responses. We subsequently two families harboring...