We report rare monoallelic variants of that alter intracellular trafficking and diminish thrombopoietin secretion. Affected cases have autosomal-dominant thrombocytopenia but no other hematological features.
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http://dx.doi.org/10.1182/bloodadvances.2019001293 | DOI Listing |
Sci Transl Med
January 2025
Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas TX, 75390, USA.
Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates transcription.
View Article and Find Full Text PDFJAMA Cardiol
January 2025
Program of Medical and Population Genetics, Broad Institute of MIT (Massachusetts Institute of Technology) and Harvard, Cambridge, Massachusetts.
Importance: Treatment to lower high levels of low-density lipoprotein cholesterol (LDL-C) reduces incident coronary artery disease (CAD) risk but modestly increases the risk for incident type 2 diabetes (T2D). The extent to which genetic factors across the cholesterol spectrum are associated with incident T2D is not well understood.
Objective: To investigate the association of genetic predisposition to increased LDL-C levels with incident T2D risk.
J Exp Med
February 2025
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.
View Article and Find Full Text PDFJID Innov
March 2025
Cell Biology & Cutaneous Research, Blizard Institute, Queen Mary University of London, London, United Kingdom.
Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa-knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies.
View Article and Find Full Text PDFAnn Clin Transl Neurol
January 2025
Department of Neurology, Movement Disorders Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Uniparental isodisomy (UPiD) can cause mixed phenotypes of imprinting disorders and autosomal-recessive diseases. We present the case of a 3-year-old male with a blended phenotype of TECPR2-related hereditary sensory and autonomic neuropathy (HSAN9) and Temple syndrome (TS14) due to maternal UPiD of chromosome 14, which includes a loss-of-function founder variant in the TECPR2 gene [NM_014844.5: c.
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