3,456 results match your criteria Wiskott-Aldrich Syndrome


Gene Therapy for Wiskott-Aldrich Syndrome: History, New Vectors, Future Directions.

J Allergy Clin Immunol 2020 Jul 2. Epub 2020 Jul 2.

Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics and Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, United States. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2020.06.018DOI Listing

Distinctive roles of Abi1 in regulating actin-associated proteins during human smooth muscle cell migration.

Sci Rep 2020 Jun 30;10(1):10667. Epub 2020 Jun 30.

Department of Molecular and Cellular Physiology, Albany Medical College, 47 New Scotland Avenue, MC-8, Albany, NY, 12208, USA.

Smooth muscle cell migration is essential for many diverse biological processes such as pulmonary/cardiovascular development and homeostasis. Abi1 (Abelson interactor 1) is an adapter protein that has been implicated in nonmuscle cell migration. However, the role and mechanism of Abi1 in smooth muscle migration are largely unknown. Read More

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http://dx.doi.org/10.1038/s41598-020-67781-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326921PMC

N-Wasp regulates oligodendrocyte myelination.

J Neurosci 2020 Jun 29. Epub 2020 Jun 29.

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

Oligodendrocytes myelination depends on actin cytoskeleton rearrangement. Neural Wiskott-Aldrich syndrome protein (N-Wasp) is an actin nucleation factor that promotes polymerization of branched actin filaments. N-Wasp activity is essential for myelin membrane wrapping by Schwann cells, but its role in oligodendrocytes and CNS myelination remains unknown. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.0912-20.2020DOI Listing

Hereditary Predisposition to Hematopoietic Neoplasms: When Bloodline Matters for Blood Cancers.

Mayo Clin Proc 2020 Jul 19;95(7):1482-1498. Epub 2020 Jun 19.

Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN. Electronic address:

With the advent of precision genomics, hereditary predisposition to hematopoietic neoplasms- collectively known as hereditary predisposition syndromes (HPS)-are being increasingly recognized in clinical practice. Familial clustering was first observed in patients with leukemia, which led to the identification of several germline variants, such as RUNX1, CEBPA, GATA2, ANKRD26, DDX41, and ETV6, among others, now established as HPS, with tendency to develop myeloid neoplasms. However, evidence for hereditary predisposition is also apparent in lymphoid and plasma--cell neoplasms, with recent discoveries of germline variants in genes such as IKZF1, SH2B3, PAX5 (familial acute lymphoblastic leukemia), and KDM1A/LSD1 (familial multiple myeloma). Read More

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http://dx.doi.org/10.1016/j.mayocp.2019.12.013DOI Listing

Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side.

Pharmaceutics 2020 Jun 13;12(6). Epub 2020 Jun 13.

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.

Recent clinical trials using patient's own corrected hematopoietic stem cells (HSCs), such as for primary immunodeficiencies (Adenosine deaminase (ADA) deficiency, X-linked Severe Combined Immunodeficiency (SCID), X-linked chronic granulomatous disease (CGD), Wiskott-Aldrich Syndrome (WAS)), have yielded promising results in the clinic; endorsing gene therapy to become standard therapy for a number of diseases. However, the journey to achieve such a successful therapy is not easy, and several challenges have to be overcome. In this review, we will address several different challenges in the development of gene therapy for immune deficiencies using our own experience with Recombinase-activating gene 1 (RAG1) SCID as an example. Read More

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http://dx.doi.org/10.3390/pharmaceutics12060549DOI Listing

WasC, a WASP family protein, is involved in cell adhesion and migration through regulation of F-actin polymerization in Dictyostelium.

J Microbiol 2020 Jun 10. Epub 2020 Jun 10.

Department of Biology & BK21- Plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Gwangju, 61452, Republic of Korea.

The actin cytoskeleton is involved in the regulation of cell morphology and migration. Wiskott-Aldrich Syndrome proteins (WASPs) play an important role in controlling actin polymerization by activating the Arp2/3 complex. The present study investigated the roles of WasC, one of the 3 WASPs in Dictyostelium, in cellular processes. Read More

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http://dx.doi.org/10.1007/s12275-020-0138-9DOI Listing

Identification of a novel WAS mutation in a South African patient presenting with atypical Wiskott-Aldrich syndrome: a case report.

BMC Med Genet 2020 Jun 5;21(1):124. Epub 2020 Jun 5.

DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa.

Background: The X-linked recessive primary immunodeficiency disease (PIDD) Wiskott-Aldrich syndrome (WAS) is identified by an extreme susceptibility to infections, eczema and thrombocytopenia with microplatelets. The syndrome, the result of mutations in the WAS gene which encodes the Wiskott-Aldrich protein (WASp), has wide clinical phenotype variation, ranging from classical WAS to X-linked thrombocytopaenia and X-linked neutropaenia. In many cases, the diagnosis of WAS in first affected males is delayed, because patients may not present with the classic signs and symptoms, which may intersect with other thrombocytopenia causes. Read More

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http://dx.doi.org/10.1186/s12881-020-01054-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275612PMC

Genetic Sequencing of Pediatric Patients Identifies Mutations in Monogenic Inflammatory Bowel Disease Genes that Translate to Distinct Clinical Phenotypes.

Clin Transl Gastroenterol 2020 Feb;11(2):e00129

Department of Human Genetics and Genomic Medicine, University of Southampton, Southampton, UK.

Objectives: Monogenic inflammatory bowel disease (IBD) comprises rare Mendelian causes of gut inflammation, often presenting in infants with severe and atypical disease. This study aimed to identify clinically relevant variants within 68 monogenic IBD genes in an unselected pediatric IBD cohort.

Methods: Whole exome sequencing was performed on patients with pediatric-onset disease. Read More

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http://dx.doi.org/10.14309/ctg.0000000000000129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145023PMC
February 2020

Successful Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide in Wiskott-Aldrich Syndrome With Myeloablative Conditioning.

J Pediatr Hematol Oncol 2020 May 26. Epub 2020 May 26.

Pediatric Hematology Oncology and Bone Marrow Transplant Unit, Cancer Institute, Medanta The Medicity Hospital, Gurgaon, Haryana, India.

Hematopoietic stem cell transplant (HSCT) is the only curative treatment modality for Wiskott-Aldrich syndrome. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) is an upcoming option in children with nonmalignant conditions. However, only few cases have been reported for Wiskott-Aldrich syndrome HSCT with PTCy approach. Read More

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http://dx.doi.org/10.1097/MPH.0000000000001841DOI Listing

[Aortic aneurysm in a patient with Wiskott-Aldrich syndrome].

Rev Alerg Mex 2020 Jan-Mar;67(1):87-93

Hospital Pediátrico de Sinaloa, Departamento de Inmunología y Alergia, Sinaloa, México.

Background: The Wiskott-Aldrich syndrome is a combined immunodeficiency associated with a syndrome linked to the X chromosome, which is characterized by eczema, recurrent infections, and thrombocytopenia. Other manifestations include autoimmune disorders such as hemolytic anemia or thrombocytopenic purpura mediated by the immune system, increased susceptibility to malignant tumors, including lymphoma or leukemia.

Clinical Case: A 7-year-old male patient with a diagnosis of Wiskott-Aldrich syndrome who was treated with intravenous gamma globulin, antimicrobial prophylaxis with trimethoprim/sulfamethoxazole, and fluconazole, as well as with prednisone and cyclosporine due to hemolytic anemia and uveitis. Read More

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http://dx.doi.org/10.29262/ram.v67i1.696DOI Listing

MicroRNA-1253 Regulation of WASF2 (WAVE2) and its Relevance to Racial Health Disparities.

Genes (Basel) 2020 May 20;11(5). Epub 2020 May 20.

Department of Biology, Morgan State University, Baltimore, MD 21251, USA.

The prevalence of hypertension among African Americans (AAs) in the US is among the highest of any demographic and affects over two-thirds of AA women. Previous data from our laboratory suggest substantial differential gene expression (DGE) of mRNAs and microRNAs (miRNAs) exists within peripheral blood mononuclear cells (PBMCs) isolated from AA and white women with or without hypertension. We hypothesized that DGE by race may contribute to racial differences in hypertension. Read More

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http://dx.doi.org/10.3390/genes11050572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288301PMC

Loss of Wasl improves pancreatic cancer outcome.

JCI Insight 2020 May 21;5(10). Epub 2020 May 21.

Klinik und Poliklinik für Innere Medizin II, Technical University of Munich, Germany.

Several studies have suggested an oncogenic role for the neural Wiskott-Aldrich syndrome protein (N-WASP, encoded by the Wasl gene), but thus far, little is known about its function in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed in silico analysis of WASL expression in PDAC patients and found a correlation between low WASL expression and prolonged survival. To clarify the role of Wasl in pancreatic carcinogenesis, we used 2 oncogenic Kras-based PDAC mouse models with pancreas-specific Wasl deletion. Read More

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http://dx.doi.org/10.1172/jci.insight.127275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259520PMC

Abl-mediated PI3K activation regulates macrophage podosome formation.

J Cell Sci 2020 Jun 8;133(11). Epub 2020 Jun 8.

School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong, Hong Kong

Podosomes play crucial roles in macrophage adhesion and migration. Wiskott-Aldrich syndrome protein (WASP; also known as WAS)-mediated actin polymerization is one of the key events initiating podosome formation. Nevertheless, membrane signals to trigger WASP activation at macrophage podosomes remain unclear. Read More

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http://dx.doi.org/10.1242/jcs.234385DOI Listing

WASF3 Knockdown Sensitizes Gastric Cancer Cells to Oxaliplatin by Inhibiting ATG12-Mediated Autophagy.

Am J Med Sci 2020 05 13;359(5):287-295. Epub 2020 Mar 13.

Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China. Electronic address:

Background: Gastric cancer is one of the most aggressive tumors, usually resulting in metastasis, and therapies for advanced gastric cancer remain limited. Drug resistance is the main reason for chemotherapeutic failure in gastric cancer. Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis of different cancers. Read More

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http://dx.doi.org/10.1016/j.amjms.2020.02.007DOI Listing

MicroRNA-93 targets WASF3 and functions as a metastasis suppressor in breast cancer.

Cancer Sci 2020 Jun 29;111(6):2093-2103. Epub 2020 May 29.

Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.

Cancer cells with cancer stem cell (CSC) properties initiate both primary tumor formation and metastases at distant sites. Acquisition of CSC properties is highly associated with epigenetic alterations, including those mediated by microRNAs (miRNAs). We have previously established the breast cancer patient-derived tumor xenograft (PDX) mouse model in which CSC marker CD44 cancer cells formed spontaneous microscopic metastases in the liver. Read More

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http://dx.doi.org/10.1111/cas.14423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293106PMC

Multiplexed Proteomic Analysis for Diagnosis and Screening of Five Primary Immunodeficiency Disorders From Dried Blood Spots.

Front Immunol 2020 1;11:464. Epub 2020 Apr 1.

Seattle Children's Research Institute, Seattle, WA, United States.

Early detection of Primary Immunodeficiencies Disorders (PIDDs) is of paramount importance for effective treatment and disease management. Many PIDDs would be strong candidates for newborn screening (NBS) if robust screening methods could identify patients from dried blood spots (DBS) during the neonatal period. As majority of congenital PIDDs result in the reduction or absence of specific proteins, direct quantification of these target proteins represents an attractive potential screening tool. Read More

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http://dx.doi.org/10.3389/fimmu.2020.00464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141245PMC

A Novel Mutation in WAS Gene Causing a Phenotypic Presentation of Wiskott-Aldrich Syndrome: A Case Report.

J Pediatr Hematol Oncol 2020 Apr 13. Epub 2020 Apr 13.

Division of Pediatric Allergy and Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago.

Background: Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by immunodeficiency, thrombocytopenia, and atopic dermatitis.

Observations: This infant presented at birth with petechiae and bruising, with severe neonatal thrombocytopenia. Genetic testing for WAS revealed a variant of unknown significance hemizygous missense mutation in the WAS gene. Read More

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http://dx.doi.org/10.1097/MPH.0000000000001790DOI Listing

Use of Thromboelastography to Guide Platelet Infusion in a Patient with Wiskott-Aldrich Syndrome Undergoing Renal Transplant.

Exp Clin Transplant 2020 Apr 7. Epub 2020 Apr 7.

From the Renal Transplant Unit, Royal Free Hospital, NHS Foundation Trust, London, United Kingdom.

Wiskott-Aldrich syndrome is a rare primary immuno-deficiency disorder that is characterized by a triad of microthrombocytopenia, eczema, and recurrent infections. Progression to end-stage renal failure is common in survivors due to immunoglobulin A nephropathy. We describe the case of a 24-year-old male with Wiskott-Aldrich syndrome. Read More

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http://dx.doi.org/10.6002/ect.2019.0347DOI Listing

Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report.

Blood 2020 Jun;135(23):2094-2105

Pediatric Allergy, Immunology, and Blood and Marrow Transplant Division, University of California, San Francisco Benioff Children's Hospital, San Francisco, CA.

Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. Read More

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http://dx.doi.org/10.1182/blood.2019002939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273831PMC

WHIMP links the actin nucleation machinery to Src-family kinase signaling during protrusion and motility.

PLoS Genet 2020 03 20;16(3):e1008694. Epub 2020 Mar 20.

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

Cell motility is governed by cooperation between the Arp2/3 complex and nucleation-promoting factors from the Wiskott-Aldrich Syndrome Protein (WASP) family, which together assemble actin filament networks to drive membrane protrusion. Here we identify WHIMP (WAVE Homology In Membrane Protrusions) as a new member of the WASP family. The Whimp gene is encoded on the X chromosome of a subset of mammals, including mice. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112243PMC

Sexual dimorphism in cardiac transcriptome associated with a troponin C murine model of hypertrophic cardiomyopathy.

Physiol Rep 2020 03;8(6):e14396

Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.

Heart disease remains the number one killer of women in the US. Nonetheless, studies in women and female animal models continue to be underrepresented in cardiac research. Hypertrophic cardiomyopathy (HCM), the most commonly inherited cardiac disorder, has been tied to sarcomeric protein variants in both sexes. Read More

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http://dx.doi.org/10.14814/phy2.14396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081104PMC

Gene therapy and genome editing for primary immunodeficiency diseases.

Genes Dis 2020 Mar 30;7(1):38-51. Epub 2019 Jul 30.

Molecular and Cellular Immunology, Great Ormond Street Institute of Child Health, University Colleage London, UK.

In past two decades the gene therapy using genetic modified autologous hematopoietic stem cells (HSCs) transduced with the viral vector has become a promising alternative option for treating primary immunodeficiency diseases (PIDs). Despite of some pitfalls at early stage clinical trials, the field of gene therapy has advanced significantly in the last decade with improvements in viral vector safety, preparatory regime for manufacturing high quality virus, automated CD34 cell purification. Hence, the overall outcome from the clinical trials for the different PIDs has been very encouraging. Read More

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http://dx.doi.org/10.1016/j.gendis.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063425PMC

Yeast as a Model to Understand Actin-Mediated Cellular Functions in Mammals-Illustrated with Four Actin Cytoskeleton Proteins.

Cells 2020 Mar 10;9(3). Epub 2020 Mar 10.

School of Medical Science, Gold Coast campus, Griffith University, Southport QLD 4222, Australia.

The budding yeast has an actin cytoskeleton that comprises a set of protein components analogous to those found in the actin cytoskeletons of higher eukaryotes. Furthermore, the actin cytoskeletons of and of higher eukaryotes have some similar physiological roles. The genetic tractability of budding yeast and the availability of a stable haploid cell type facilitates the application of molecular genetic approaches to assign functions to the various actin cytoskeleton components. Read More

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http://dx.doi.org/10.3390/cells9030672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140605PMC

[Immunodeficiency diseases with interstitial lung disease as major clinical manifestations: report of six cases].

Zhonghua Er Ke Za Zhi 2020 Mar;58(3):228-232

Department of Respiratory Disease, Shenzhen Children's Hospital, Shenzhen 518038, China.

To summarize the clinical features of immunodeficiency diseases with interstitial lung disease (ILD) as major clinical manifestations and to improve understanding etiology of ILD. The clinical features and clinical clues for diagnosis of six cases with immunodeficiency presented with ILD in Shenzhen Children's Hospital from January 2014 to December 2016 were retrospectively analyzed. The patients' age ranged from 3 months to 5 years and 9 months, 5 cases were male. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0578-1310.2020.03.013DOI Listing

A Homozygous Mutation in 5' Untranslated Region of TNFRSF11A Leading to Molecular Diagnosis of Osteopetrosis Coinheritance With Wiskott-Aldrich Syndrome.

J Pediatr Hematol Oncol 2020 Feb 24. Epub 2020 Feb 24.

The Rina Zaizov Division of Pediatric Hematology-Oncology, Schneider Children's Medical Center, Petah Tikva, Israel.

Wiskott-Aldrich syndrome (WAS) and osteopetrosis are 2 different, rare hereditary diseases. Here we report clinical and molecular genetics investigations on an infant patient with persistent thrombocytopenia and prolonged fever. He was clinical diagnosed as osteopetrosis according to clinical presentation, radiologic skeletal features, and bone biopsy results. Read More

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http://dx.doi.org/10.1097/MPH.0000000000001760DOI Listing
February 2020

The evaluation of malignancies in Turkish primary immunodeficiency patients; a multicenter study.

Pediatr Allergy Immunol 2020 Feb 14. Epub 2020 Feb 14.

Division of Pediatric Allergy and Clinical Immunology, Uludag University Faculty of Medicine, Bursa, Turkey.

Background: There are no data regarding the prevalence of malignancies in patients with primary immunodeficiency (PID) in Turkey. Along with the prevalence of malignancy, we aimed to present the types of malignancy and define the underlying immune deficiency of the patients.

Method: Between the years 1992 and 2018, from five tertiary immunology clinics, fifty-nine patients with PID who developed malignancy were included. Read More

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http://dx.doi.org/10.1111/pai.13231DOI Listing
February 2020

WASP and Mst1 coregulate B-cell development and B-cell receptor signaling.

Blood Adv 2020 Feb;4(3):573-585

Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.

Mst1 is a serine/threonine kinase involved in cell survival, proliferation, apoptosis, and tumorigenesis. In mice, Mst1 regulates actin dynamics required for T-cell adhesion and migration, which correlate with thymic egress and entry into lymphatic tissue. The role of Mst1 in B cells and how it may control actin-dependent processes has not been well characterized. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013255PMC
February 2020

[Ileitis as presentation of lymphoma in Wiskott-Aldrich syndrome].

Medicina (B Aires) 2020 ;80(1):81-83

Departamento de Medicina Interna, Hospital Italiano de Buenos Aires, Hospital Italiano de Buenos Aires, Argentina. E-mail:

Wiskott-Aldrich syndrome is a rare X chromosome-linked primary immunodeficiency syndrome associated with an increased incidence of infections, autoimmune disorders and neoplasms. We present the case of a 41-year-old man with a diagnosis of Wiskott-Aldrich syndrome with ileitis as a form of presentation of a lymphoproliferative syndrome. The ileitis, in the context of the patient, represents a clinical challenge given the large number of differential diagnoses (inflammatory bowel disease, infections, neoplasms and lymphoproliferative diseases), so it usually requires anatomopathological diagnosis and particular considerations regarding the subsequent specific treatment. Read More

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Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs.

Blood 2020 Apr;135(15):1219-1231

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA.

In gene therapy with human hematopoietic stem and progenitor cells (HSPCs), each gene-corrected cell and its progeny are marked in a unique way by the integrating vector. This feature enables lineages to be tracked by sampling blood cells and using DNA sequencing to identify the vector integration sites. Here, we studied 5 cell lineages (granulocytes, monocytes, T cells, B cells, and natural killer cells) in patients having undergone HSPC gene therapy for Wiskott-Aldrich syndrome or β hemoglobinopathies. Read More

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http://dx.doi.org/10.1182/blood.2019002350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146019PMC

A Novel Mutation in a Patient with Wiskott-Aldrich Syndrome

Turk J Haematol 2020 05 29;37(2):128-129. Epub 2020 Jan 29.

İnönü University Faculty of Medicine, Division of Medical Genetics, Malatya, Turkey

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http://dx.doi.org/10.4274/tjh.galenos.2020.2019.0321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236416PMC

Dental management of a child with Wiskott Aldrich syndrome prior to bone marrow transplant: A case report.

Spec Care Dentist 2020 Mar 29;40(2):206-210. Epub 2020 Jan 29.

Department of Pediatric and Preventive Dentistry, Nair Hospital Dental College, Mumbai, Mahrashtra, India.

Aim: Orodental manifestations are commonly presented in Wiskott Aldrich Syndrome (WAS). The purpose of this paper is to report a case of dental management of a 5-year-old male child with WAS before Hematopoietic Stem Cell Transplantation (HSCT). Such patients are more prone to infection due to pretransplantation chemotherapy and posttransplantation immunosuppression; thus, it becomes imperative to eliminate all potential sources of infection before transplantation. Read More

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http://dx.doi.org/10.1111/scd.12452DOI Listing

WASP family proteins regulate the mobility of the B cell receptor during signaling activation.

Nat Commun 2020 01 23;11(1):439. Epub 2020 Jan 23.

Biophysics Program, University of Maryland, College Park, MD, 20742, USA.

Regulation of membrane receptor mobility tunes cellular response to external signals, such as in binding of B cell receptors (BCR) to antigen, which initiates signaling. However, whether BCR signaling is regulated by BCR mobility, and what factors mediate this regulation, are not well understood. Here we use single molecule imaging to examine BCR movement during signaling activation and a novel machine learning method to classify BCR trajectories into distinct diffusive states. Read More

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http://dx.doi.org/10.1038/s41467-020-14335-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978525PMC
January 2020

Neuronal Wiskott-Aldrich syndrome protein regulates Pseudomonas aeruginosa-induced lung vascular permeability through the modulation of actin cytoskeletal dynamics.

FASEB J 2020 Feb 9;34(2):3305-3317. Epub 2020 Jan 9.

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Pulmonary edema associated with increased vascular permeability is a severe complication of Pseudomonas (P.) aeruginosa-induced acute lung injury. The mechanisms underlying P aeruginosa-induced vascular permeability are not well understood. Read More

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http://dx.doi.org/10.1096/fj.201902915RDOI Listing
February 2020

Ste20-like Kinase-mediated Control of Actin Polymerization Is a New Mechanism for Thin Filament-associated Regulation of Airway Smooth Muscle Contraction.

Am J Respir Cell Mol Biol 2020 May;62(5):645-656

Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York.

It has been reported that actin polymerization is regulated by protein tyrosine phosphorylation in smooth muscle on contractile stimulation. The role of protein serine/threonine phosphorylation in modulating actin dynamics is underinvestigated. SLK (Ste20-like kinase) is a serine/threonine protein kinase that plays a role in apoptosis, cell cycle, proliferation, and migration. Read More

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http://dx.doi.org/10.1165/rcmb.2019-0310OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193783PMC

Hereditary spastic paraplegia SPG8 mutations impair CAV1-dependent, integrin-mediated cell adhesion.

Sci Signal 2020 01 7;13(613). Epub 2020 Jan 7.

Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.

Mutations in (also known as ) cause autosomal dominant hereditary spastic paraplegia (HSP) type SPG8. WASHC5, commonly called strumpellin, is a core component of the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex that activates actin nucleation at endosomes. Although various other cellular roles for strumpellin have also been described, none account for how SPG8-associated mutations lead to HSP. Read More

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http://dx.doi.org/10.1126/scisignal.aau7500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231525PMC
January 2020

Cytoskeletal tension actively sustains the migratory T-cell synaptic contact.

EMBO J 2020 Mar 2;39(5):e102783. Epub 2020 Jan 2.

Koch Institute of Integrative Research, MIT, Cambridge, MA, USA.

When migratory T cells encounter antigen-presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T-cell immunity. While the cellular processes underlying synapse formation have been well characterized, those that maintain the symmetry, and thereby the stability of the synapse, remain unknown. Here we identify an antigen-triggered mechanism that actively promotes T-cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott-Aldrich syndrome protein (WASP), and contraction of the resultant actin filaments by myosin II. Read More

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http://dx.doi.org/10.15252/embj.2019102783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049817PMC

αII-spectrin controls calcium-regulated exocytosis in neuroendocrine chromaffin cells through neuronal Wiskott-Aldrich Syndrome protein interaction.

IUBMB Life 2020 Apr 20;72(4):544-552. Epub 2019 Dec 20.

Centre National de la Recherche Scientifique, Institut des Neurosciences Cellulaires et Intégratives, Université de Strasbourg, Strasbourg, France.

Besides a fundamental structural role at the plasma membrane, spectrin- and actin-based skeletons have been proposed to participate in various processes including vesicular trafficking. Neuroendocrine cells release hormones and neuropeptides through calcium-regulated exocytosis, a process that is coordinated by a fine remodeling of the actin cytoskeleton. We describe here that calcium-regulated exocytosis is impaired in chromaffin and PC12 cells with reduced αII-spectrin expression levels. Read More

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http://dx.doi.org/10.1002/iub.2217DOI Listing

Gene therapy for severe combined immunodeficiencies and beyond.

J Exp Med 2020 Jan;217(2)

Unité de Technologies Chimiques et Biologiques pour la Santé, UMR8258 Centre National de la Recherche Scientifique - U1267 Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie de Paris, Université Paris Descartes, Paris, France.

Ex vivo retrovirally mediated gene therapy has been shown within the last 20 yr to correct the T cell immunodeficiency caused by γc-deficiency (SCID X1) and adenosine deaminase (ADA) deficiency. The rationale was brought up by the observation of the revertant of SCIDX1 and ADA deficiency as a kind of natural gene therapy. Nevertheless, the first attempts of gene therapy for SCID X1 were associated with insertional mutagenesis causing leukemia, because the viral enhancer induced transactivation of oncogenes. Read More

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http://dx.doi.org/10.1084/jem.20190607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041706PMC
January 2020

Treatment of primary immunodeficiency with allogeneic transplant and gene therapy.

Authors:
Sung-Yun Pai

Hematology Am Soc Hematol Educ Program 2019 12;2019(1):457-465

Division of Pediatric Hematology-Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA.

The treatment of primary immunodeficiency disorders with allogeneic hematopoietic cell transplantation (HCT) has a history dating back to 1968 with the first successful transplant for a patient with severe combined immunodeficiency (SCID). The omission of conditioning for patients with SCID owing to their inability to reject allogeneic grafts and the increasing use of reduced intensity conditioning regimens often result in a state of mixed or split donor-recipient chimerism. The use of gene therapy (GT) via retroviral or lentiviral transduction of autologous CD34+ hematopoietic stem and progenitor cells is expected to correct only a portion of the hematopoietic stem cell compartment. Read More

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http://dx.doi.org/10.1182/hematology.2019000052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913427PMC
December 2019

Orai1 Promotes Osteosarcoma Metastasis by Activating the Ras-Rac1-WAVE2 Signaling Pathway.

Med Sci Monit 2019 Dec 4;25:9227-9236. Epub 2019 Dec 4.

Department of Spinal Surgery, Hong Hui Hospital, Xi'an Jiao Tong University, Xi'an, Shaanxi, China (mainland).

BACKGROUND The purpose of this study was to investigate whether Orai1 plays a role in the metastasis of osteosarcoma. MATERIAL AND METHODS The expression of Orai1 was silenced by small interfering RNAs against Orai1 (Orai1 siRNA) in osteosarcoma MG-63 cells. Various experiments were carried out to detect the changes in migration, invasion, and adhesion ability of these osteosarcoma cells. Read More

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http://dx.doi.org/10.12659/MSM.919594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909920PMC
December 2019

WASP Restricts Active Rac to Maintain Cells' Front-Rear Polarization.

Curr Biol 2019 12 27;29(24):4169-4182.e4. Epub 2019 Nov 27.

CRUK Beatson Institute, Switchback Road, Bearsden G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.

Efficient motility requires polarized cells, with pseudopods at the front and a retracting rear. Polarization is maintained by restricting the pseudopod catalyst, active Rac, to the front. Here, we show that the actin nucleation-promoting factor Wiskott-Aldrich syndrome protein (WASP) contributes to maintenance of front-rear polarity by controlling localization and cellular levels of active Rac. Read More

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http://dx.doi.org/10.1016/j.cub.2019.10.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926487PMC
December 2019

Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL, and NCK1.

Elife 2019 11 26;8. Epub 2019 Nov 26.

Department of Molecular Microbiology, Pathology and Immunology, School of Medicine, Washington University, St. Louis, United States.

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes, , , and , in infection by multiple picornaviruses. CRISPR deletion of , or reduced encephalomyocarditis virus (EMCV), coxsackievirus B3 (CVB3), poliovirus and enterovirus D68 infection, and chemical inhibitors of TNK2 and WASL decreased EMCV infection. Read More

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http://dx.doi.org/10.7554/eLife.50276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904212PMC
November 2019
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N-WASP knockdown upregulates inflammatory cytokines expression in human gingival fibroblasts.

Arch Oral Biol 2020 Feb 9;110:104605. Epub 2019 Nov 9.

Department of Periodontology, School and Hospital of Stomatology, Shandong University & Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China. Electronic address:

Objective: The neuronal wiskott-aldrich syndrome protein (N-WASP) is a member of the wiskott-aldrich syndrome protein (WASP) family. N-WASP plays a vital role in promoting cell migration, receptor signaling and immune inflammatory responses. This study aimed to observe the changes in the expression of inflammatory factors and involving pathways after N-WASP knockdown in human gingival fibroblasts (HGFs). Read More

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http://dx.doi.org/10.1016/j.archoralbio.2019.104605DOI Listing
February 2020

Child with Wiskott-Aldrich syndrome underwent atypical immune reconstruction after umbilical cord blood transplantation: A case report.

World J Clin Cases 2019 Nov;7(21):3622-3631

Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.

Background: Timely reconstitution of a donor-derived immune system is important for recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a case of Wiskott-Aldrich syndrome (WAS) treated by umbilical cord blood transplantation (UCBT) with atypical immune reconstruction.

Case Summary: A 1-year-old Chinese male infant was diagnosed with WAS. Read More

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http://dx.doi.org/10.12998/wjcc.v7.i21.3622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854412PMC
November 2019

Wiskott-Aldrich Syndrome (WAS) and Dedicator of Cytokinesis 8- (DOCK8) Deficiency.

Front Pediatr 2019 5;7:451. Epub 2019 Nov 5.

National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, United States.

Both Wiskott-Aldrich syndrome (WAS) and dedicator of cytokinesis 8 (DOCK8) deficiency are primary immunodeficiency diseases caused by mutations in genes that result in defective organization of the cytoskeleton in hematopoietic tissues. They share some overlapping features such as a combined immunodeficiency, eczema and a predisposition to autoimmunity and malignancy, but also have some unique features that make them relatively easy to diagnose by clinical means. Both diseases can be cured by HSCT in a large proportion of patients. Read More

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http://dx.doi.org/10.3389/fped.2019.00451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848221PMC
November 2019