3,561 results match your criteria Wiskott-Aldrich Syndrome


Hematopoietic Stem Cell Therapy for Wiskott-Aldrich Syndrome: Improved Outcome and Quality of Life.

J Blood Med 2021 11;12:435-447. Epub 2021 Jun 11.

Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.

The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder caused by mutations in the gene resulting in congenital thrombocytopenia, eczema, recurrent infections and an increased incidence of autoimmune diseases and malignancies. Without curative therapies, affected patients have diminished life expectancy and reduced quality of life. Since WAS protein (WASP) is constitutively expressed only in hematopoietic stem cell-derived lineages, hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are well suited to correct the hematologic and immunologic defects. Read More

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Intracellular artificial supramolecules based on de novo designed Y15 peptides.

Nat Commun 2021 06 7;12(1):3412. Epub 2021 Jun 7.

School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Kanagawa, Japan.

De novo designed self-assembling peptides (SAPs) are promising building blocks of supramolecular biomaterials, which can fulfill a wide range of applications, such as scaffolds for tissue culture, three-dimensional cell culture, and vaccine adjuvants. Nevertheless, the use of SAPs in intracellular spaces has mostly been unexplored. Here, we report a self-assembling peptide, Y15 (YEYKYEYKYEYKYEY), which readily forms β-sheet structures to facilitate bottom-up synthesis of functional protein assemblies in living cells. Read More

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Clinical, Laboratory Features and Clinical Courses of Patients with Wiskott Aldrich Syndrome and X-linked Thrombocytopenia-A single center study.

Immunol Invest 2021 Jun 7:1-12. Epub 2021 Jun 7.

Institute of Child Health, Division of Immunology, Hacettepe University Medical School, Ankara, Turkey.

: Wiskott Aldrich Syndrome is an X-linked primary immunodeficiency disorder characterized by microthrombocytopenia, severe immunodeficiency, and eczema. To define clinical-laboratory features, genetic defects (known/novel) of 23 patients of Wiskott Aldrich Syndrome/X-linked Thrombocytopenia (WAS/XLT) cohort, establish relationships between molecular defects and clinical features if present, evaluate patients who underwent hematopoietic stem cell transplantation (HSCT) and did not. Qualitative analysis from patients' hospital files and Sanger sequencing for molecular diagnosis was performed. Read More

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Screening and functional verification of the target protein of pedunsaponin A in the killing of Pomacea canaliculata.

Ecotoxicol Environ Saf 2021 Sep 5;220:112393. Epub 2021 Jun 5.

College of Agronomy, Sichuan Agricultural University, Chengdu, Sichuan, China. Electronic address:

Previous study found that pedunsaponin A (PA) influenced the cytoskeleton of Pomacea canaliculata hemocytes, leading to depolarization and haemocyte destruction and eventually to snail death. In this study, we analysed the changes in protein expression by iTRAQ-mediated proteomics and identified 51 downregulated proteins. Among these, we focused on proteins related to cytoskeletal function and identified neural Wiskott-Aldrich syndrome isoform X1 (PcnWAS). Read More

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September 2021

Successful low-dose chemotherapy for refractory Epstein-Barr virus-related post-transplant lymphoproliferative disorder following hematopoietic stem cell transplantation in a child with Wiskott-Aldrich syndrome.

Clin Case Rep 2021 May 24;9(5):e04111. Epub 2021 May 24.

Department of Gynaecology Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science and Technology Wuhan China.

We report the first case of a 12-year-old boy with Wiskott-Aldrich syndrome who developed CD20-weakly expressed and CD30-highly expressed Epstein-Barr virus-related post-transplant lymphoproliferative disorder refractory to rituximab treatment. The patient was effectively and safely treated with personalized low-dose chemotherapy and subsequently remained in complete remission for 1 year. Read More

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Self-DNA Sensing by cGAS-STING and TLR9 in Autoimmunity: Is the Cytoskeleton in Control?

Front Immunol 2021 18;12:657344. Epub 2021 May 18.

Cellular Immunology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

Modified or misplaced DNA can be recognized as a danger signal by mammalian cells. Activation of cellular responses to DNA has evolved as a defense mechanism to microbial infections, cellular stress, and tissue damage, yet failure to control this mechanism can lead to autoimmune diseases. Several monogenic and multifactorial autoimmune diseases have been associated with type-I interferons and interferon-stimulated genes (ISGs) induced by deregulated recognition of self-DNA. Read More

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Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy.

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

School of Life Science, Beijing Institute of Technology, No. 5 Zhongguancun South Street, Haidian District, Beijing 100081, China.

The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Read More

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[WASH regulates alternative splicing and gene transcription by interacting with hnRNP A1].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jun;37(6):507-512

Laboratory of Protein Structure and Function, Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar 161000, China. *Corresponding authors, E-mail:

Objective To investigate the interaction between Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) and heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and its biological functions. Methods The interaction between WASH/FAM21, the core member of WASH complex, and hnRNP A1 was identified by mass spectrometry and co-immunoprecipitation. Telomere lengths of shWASH and shScramble cells were measured by Real-time qPCR. Read More

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Gastroblastoma with a novel EWSR1-CTBP1 fusion presenting in adolescence.

Genes Chromosomes Cancer 2021 May 26. Epub 2021 May 26.

Department of Pathology, The Ohio State University, Columbus, Ohio, USA.

Gastroblastomas are rare tumors with a biphasic epithelioid/spindle cell morphology that typically present in early adulthood and have recurrent MALAT1-GLI1 fusions. We describe an adolescent patient with Wiskott-Aldrich syndrome who presented with a large submucosal gastric tumor with biphasic morphology. Despite histologic features consistent with gastroblastoma, a MALAT1-GLI1 fusion was not found in this patient's tumor; instead, comprehensive molecular profiling identified a novel EWSR1-CTBP1 fusion and no other significant genetic alterations. Read More

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Mitochondria transfer from early stages of erythroblasts to their macrophage niche via tunnelling nanotubes.

Br J Haematol 2021 Jun 25;193(6):1260-1274. Epub 2021 May 25.

Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Adult erythropoiesis entails a series of well-coordinated events that produce mature red blood cells. One of such events is the mitochondria clearance that occurs cell-autonomously via autophagy-dependent mechanisms. Interestingly, recent studies have shown mitochondria transfer activities between various cell types. Read More

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WAVE regulatory complex.

Curr Biol 2021 May;31(10):R512-R517

Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, 3110 Molecular Biology Building, Ames, IA, USA. Electronic address:

Dynamic rearrangement of the actin cytoskeleton drives a myriad of processes in eukaryotic cells, such as cell migration and vesicle trafficking, and its dysregulation is deeply associated with various diseases, including cancer, immune deficiency, and neurological disorders. Members of the Wiskott-Aldrich syndrome protein (WASP) family, including WASP, N-WASP, WAVE, WASH, WHAMM, JMY, and the recently identified WHIMP, are ubiquitous regulators of actin dynamics. Although each WASP-family protein uses a different regulatory mechanism and participates in distinct cellular processes, they all act by integrating various upstream signals and transmitting them to their carboxy-terminal WCA (WH2-central-acidic, where WH2 stands for WASP homology 2) domain. Read More

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[Improvement in platelet count and bleeding symptom during treatment with eltrombopag in a patient with X-linked thrombocytopenia].

Rinsho Ketsueki 2021 ;62(4):257-261

Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University.

Herein, we describe a 13-year-old male adolescent who had chronic thrombocytopenia since infancy. In this case, X-linked thrombocytopenia (XLT) was suspected owing to a family history of chronic thrombocytopenia and small-sized platelets. Moreover, the patient was refractory to immunoglobulin therapy. Read More

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Novel CTRP8-RXFP1-JAK3-STAT3 axis promotes Cdc42-dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells.

Mol Oncol 2021 May 7. Epub 2021 May 7.

Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, Canada.

C1q tumor necrosis factor-related peptide 8 (CTRP8) is the least studied member of the C1Q-TNF-related peptide family. We identified CTRP8 as a ligand of the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1) in glioblastoma multiforme (GBM). The CTRP8-RXFP1 ligand-receptor system protects human GBM cells against the DNA-alkylating damage-inducing temozolomide (TMZ), the drug of choice for the treatment of patients with GBM. Read More

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Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India.

Front Immunol 2021 16;12:627651. Epub 2021 Apr 16.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Read More

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Platelet function and bleeding at different phases of childhood immune thrombocytopenia.

Sci Rep 2021 Apr 30;11(1):9401. Epub 2021 Apr 30.

National Medical Research Center of Pediatric Hematology, Oncology and Immunology Named After Dmitry Rogachev, Russian Ministry of Healthcare, 1 Samory Mashela Str, Moscow, Russia, 117997.

Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. Read More

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Role of Thrombopoietin Receptor Agonists in Inherited Thrombocytopenia.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Department of Hematology and Oncology, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Arrixaca, CIBERER-U765, 30008 Murcia, Spain.

In the last decade, improvements in genetic testing have revolutionized the molecular diagnosis of inherited thrombocytopenias (ITs), increasing the spectrum of knowledge of these rare, complex and heterogeneous disorders. In contrast, the therapeutic management of ITs has not evolved in the same way. Platelet transfusions have been the gold standard treatment for a long time. Read More

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A Clinical Diagnosis of Wiskott Aldrich Syndrome in an Ethiopian Boy with Recurrent Sinopulmonary Infections: A Case Report.

Ethiop J Health Sci 2020 Nov;30(6):1051-1054

St. Paul's Hospital and Millennium Medical College, Addis Ababa, Ethiopia.

Background: Wiskott Aldrich syndrome is a primary immunodeficiency notable for eczema, recurrent infections, bleeding diathesis and microcytic thrombocytopenia.

Case: A 4½ year old boy presented with recurrent sinopulmonary infections, repeated treatment for severe eczema since infancy, thrombocytopenia with low platelet volume. His brother and uncles died during childhood due to repeated illnesses. Read More

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November 2020

Clinical and genetic analysis of 2 rare cases of Wiskott-Aldrich syndrome from Chinese minorities: Two case reports.

Medicine (Baltimore) 2021 Apr;100(16):e25527

Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics.

Rationale: Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities. Read More

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The actin nucleation factors JMY and WHAMM enable a rapid Arp2/3 complex-mediated intrinsic pathway of apoptosis.

PLoS Genet 2021 Apr 19;17(4):e1009512. Epub 2021 Apr 19.

Department of Molecular and Cell Biology, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, United States of America.

The actin cytoskeleton is a well-known player in most vital cellular processes, but comparably little is understood about how the actin assembly machinery impacts programmed cell death pathways. In the current study, we explored roles for the human Wiskott-Aldrich Syndrome Protein (WASP) family of actin nucleation factors in DNA damage-induced apoptosis. Inactivation of each WASP-family gene revealed that two of them, JMY and WHAMM, are necessary for rapid apoptotic responses. Read More

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Dermoscopic Features of Giant Molluscum Contagiosum in a Patient with Acquired Immunodeficiency Syndrome.

Acta Dermatovenerol Croat 2020 Dec;28(7):233-235

Martyna Sławińska MD, PhD, Department of Dermatology, Venereology and Allergology Medical University of Gdańsk, Smoluchowskiego 17 Street, 80-214 Gdańsk;

Giant molluscum contagiosum (MC) is a peculiar variant of the disease with the presence of multiple or single lesions larger than 5 mm. In contrast to typical molluscum contagiosum, dermoscopic features of giant lesions have been poorly described, and none of the reports included multiple giant lesions in an immunocompromised patient. We present a patient with acquired immunodeficiency syndrome diagnosed with multiple giant molluscum contagiosum along with the dermoscopic features of this entity. Read More

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December 2020

Successful Allogeneic Peripheral Blood Stem Cell Transplantation in 4 Wiskott-Aldrich Syndrome Patients.

J Pediatr Hematol Oncol 2021 Apr 6. Epub 2021 Apr 6.

Hematology and Bone Marrow Transplant Department, Pierre and Marie Curie Center, Algiers, Algeria.

Background: Allogeneic hematopoietic stem cell transplantation is a potential curative treatment in Wiskott-Aldrich syndrome (WAS). Here, we analyzed the outcomes in 4 WAS patients who underwent this procedure with peripheral blood stem cell (PBSC) in our center.

Patients And Methods: Four patients with severe WAS phenotype have received allogeneic hematopoietic stem cell transplantation between January 2014 and December 2019 from matched sibling donors with PBSC. Read More

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Dragon's Blood Regulates Rac1-WAVE2-Arp2/3 Signaling Pathway to Protect Rat Intestinal Epithelial Barrier Dysfunction Induced by Simulated Microgravity.

Int J Mol Sci 2021 Mar 8;22(5). Epub 2021 Mar 8.

School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing 100081, China.

Dragon's Blood is a red resin from Dracaena cochinchinensis (Lour.) S.C. Read More

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Acquired Thrombotic Thrombocytopenic Purpura in a 5-Year-Old Child With Wiskott-Aldrich Syndrome.

J Pediatr Hematol Oncol 2021 Mar 23. Epub 2021 Mar 23.

Department of Pediatrics, Division of Allergy and Immunology Division of Hematology and Oncology, Research and Training Hospital of Sakarya University, Adapazari, Sakarya Bursa City Hospital, Medical Genetics, Bursa, Türkiye.

Thrombocytopenia is often seen as a laboratory finding during childhood. A supposed idiopathic thrombocytopenic purpura patient who was later diagnosed as Wiskott-Aldrich syndrome (WAS) and developed acquired thrombotic thrombocytopenic purpura (aTTP). Although autoimmune manifestations in WAS described, aTTP was reported just once. Read More

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WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity.

Science 2021 03;371(6536)

Mount Sinai Hospital, Toronto, Ontario, Canada.

Cytoskeletal regulatory protein dysfunction has been etiologically linked to inherited diseases associated with immunodeficiency and autoimmunity, but the mechanisms involved are incompletely understood. Here, we show that conditional ablation in T cells causes severe autoimmunity associated with increased mammalian target of rapamycin (mTOR) activation and metabolic reprogramming that engender spontaneous activation and accelerated differentiation of peripheral T cells. These mice also manifest diminished antigen-specific T cell responses associated with increased inhibitory receptor expression, dysregulated mitochondrial function, and reduced cell survival upon activation. Read More

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Genetic disruption of WASHC4 drives endo-lysosomal dysfunction and cognitive-movement impairments in mice and humans.

Elife 2021 03 22;10. Epub 2021 Mar 22.

Department of Neurobiology, Duke University School of Medicine, Durham, United States.

Mutation of the Wiskott-Aldrich syndrome protein and SCAR homology (WASH) complex subunit, SWIP, is implicated in human intellectual disability, but the cellular etiology of this association is unknown. We identify the neuronal WASH complex proteome, revealing a network of endosomal proteins. To uncover how dysfunction of endosomal SWIP leads to disease, we generate a mouse model of the human mutation. Read More

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Glioma pathogenesis-related protein 1 performs dual functions in tumor cells.

Cancer Gene Ther 2021 Mar 19. Epub 2021 Mar 19.

Department of Biochemistry and Molecular Biology, Jiangsu University School of Medicine, Zhenjiang, 212013, Jiangsu, China.

Glioma pathogenesis-related protein 1 (GLIPR1) was identified as an oncoprotein in some cancer types including gliomas, breast cancers, melanoma cancers, and Wilms tumors, but as a tumor suppressor in some other types of cancers, such as prostate cancers, lung cancers, bladder cancers, and thyroid cancers. In gliomas, GLIPR1 promotes the migration and invasion of glioma cells by interaction with the actin polymerization regulator Neural Wiskott-Aldrich syndrome protein (N-WASP) and then abolishes the negative effects of Heterogeneous nuclear ribonuclear protein K (hnRNPK). In prostate cancers, high levels of GLIPR1 induce apoptosis and destruction of oncoproteins. Read More

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Gene Therapies for Primary Immune Deficiencies.

Front Immunol 2021 25;12:648951. Epub 2021 Feb 25.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Gene therapy is an innovative treatment for Primary Immune Deficiencies (PIDs) that uses autologous hematopoietic stem cell transplantation to deliver stem cells with added or edited versions of the missing or malfunctioning gene that causes the PID. Initial studies of gene therapy for PIDs in the 1990-2000's used integrating murine gamma-retroviral vectors. While these studies showed clinical efficacy in many cases, especially with the administration of marrow cytoreductive conditioning before cell re-infusion, these vectors caused genotoxicity and development of leukoproliferative disorders in several patients. Read More

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February 2021

FLI1 Induces Megakaryopoiesis Gene Expression Through WAS/WIP-Dependent and Independent Mechanisms; Implications for Wiskott-Aldrich Syndrome.

Front Immunol 2021 26;12:607836. Epub 2021 Feb 26.

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.

Wiskott-Aldrich Syndrome, WAS/WAVE, is a rare, X-linked immune-deficiency disease caused by mutations in the gene, which together with its homolog, N-, regulates actin cytoskeleton remodeling and cell motility. WAS patients suffer from microthrombocytopenia, characterized by a diminished number and size of platelets, though the underlying mechanism is not fully understood. Here, we identified FLI1 as a direct transcriptional regulator of and its binding partner . Read More

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February 2021

Paroxysmal, exercise-induced, diurnally fluctuating dystonia: Expanding the phenotype of SPG8.

Parkinsonism Relat Disord 2021 Apr 17;85:26-28. Epub 2021 Feb 17.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.

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Acquired Hemophilia A in Wiskott-Aldrich Syndrome.

J Clin Immunol 2021 Mar 3. Epub 2021 Mar 3.

Department of Rheumatology and Immunology, Shenzhen Children's Hospital, China Medical University, 7019 Yitian Road, Shenzhen, 518038, China.

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