3,319 results match your criteria Wiskott-Aldrich Syndrome


[Efficacy Analysis of Unrelated Umbilical Cord Blood Transplantation for the Treatment of Wiskott-Aldrich Syndrome].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Dec;26(6):1816-1821

Department of Hematology,Zhongda Hospital,Southeast University,Nanjing 210009,Jiangsu Province, China.

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) for the treatment of Wiskott-Aldrich syndrome(WAS).

Methods: Five pediatric patients with WAS received single UCBT were retrospectively analyzed. The median age of these male patients was 268 days (range, 3 days -695 days). Read More

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December 2018

Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma.

Nat Med 2018 Dec 3. Epub 2018 Dec 3.

Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

In T lymphocytes, the Wiskott-Aldrich Syndrome protein (WASP) and WASP-interacting-protein (WIP) regulate T cell antigen receptor (TCR) signaling, but their role in lymphoma is largely unknown. Here we show that the expression of WASP and WIP is frequently low or absent in anaplastic large cell lymphoma (ALCL) compared to other T cell lymphomas. In anaplastic lymphoma kinase-positive (ALK+) ALCL, WASP and WIP expression is regulated by ALK oncogenic activity via its downstream mediators STAT3 and C/EBP-β. Read More

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December 2018
1 Read

Membrane trafficking RNA interference screen identifies a crucial role of the clathrin endocytic pathway and ARP2/3 complex for Japanese encephalitis virus infection in HeLa cells.

J Gen Virol 2018 Nov 29. Epub 2018 Nov 29.

3​Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad, Haryana, India.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is one of the leading global causes of virus-induced encephalitis. The infectious life-cycle of viruses is heavily dependent on the host membrane trafficking network. Here, we have performed a RNA-interference-based screen using a siRNA panel targeting 136 membrane trafficking proteins to identify the key regulators of JEV infection in HeLa cells. Read More

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November 2018

Dip1 Co-opts Features of Branching Nucleation to Create Linear Actin Filaments that Activate WASP-Bound Arp2/3 Complex.

Curr Biol 2018 Dec 21;28(23):3886-3891.e4. Epub 2018 Nov 21.

Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, 1229 University of Oregon, Eugene, OR 97403, USA. Electronic address:

When activated by Wiskott-Aldrich syndrome proteins (WASP), Arp2/3 complex nucleates branched actin filaments important for processes like cellular motility and endocytosis [1]. WASP-mediated activation of Arp2/3 complex requires a preformed actin filament, ensuring that activation by WASP creates branched instead of linear filaments. However, this biochemical requirement also means that assembly of branched actin networks must be primed with an initial seed filament [2-4]. Read More

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December 2018
1 Read

Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries.

J Clin Immunol 2018 Nov 24. Epub 2018 Nov 24.

Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. Read More

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November 2018
5 Reads

The Phenotype and Treatment of WIP Deficiency: Literature Synopsis and Review of a Patient With Pre-transplant Serial Donor Lymphocyte Infusions to Eliminate CMV.

Front Immunol 2018 2;9:2554. Epub 2018 Nov 2.

Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.

Early diagnosis of primary immunodeficiency disorders (PID) is vital and allows directed treatment, especially in syndromes with severe or profound combined immunodeficiency. In PID patients with perinatal CMV or other opportunistic, invasive infections (e.g. Read More

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November 2018
8 Reads

WASH Regulates Glucose Homeostasis by Facilitating Glut2 Receptor Recycling in Pancreatic Beta Cells.

Diabetes 2018 Nov 13. Epub 2018 Nov 13.

Division of Oncology Research and Schulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN 55905

WASH is an endosomal protein belonging to the Wiskott-Aldrich syndrome protein superfamily that participates in endosomal receptor trafficking by facilitating tubule fission via activation of the ubiquitously expressed Arp2/3 complex. While several studies have begun to understand the functions of WASH in cells lines, the in vivo function of WASH has not been fully elucidated since total body deletion in mice leads to early embryonic lethality. To circumvent this problem, we have used a WASH conditional knockout mouse model to investigate the role of WASH in the pancreas. Read More

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November 2018
5 Reads

Cutaneous Manifestations of Primary Immunodeficiency Diseases in Tunisian Children.

Mediterr J Hematol Infect Dis 2018 1;10(1):e2018065. Epub 2018 Nov 1.

Pediatric Immunohematology Department, Bone Marrow Transplantation Center Tunis, Tunisia.

Skin manifestations are frequent among patients with primary immunodeficiency diseases (PIDs). Their prevalence varies according to the type of immunodeficiency. This review provides the reader with an up-to-date summary of the common dermatologic manifestations of PIDs among Tunisian children. Read More

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November 2018
2 Reads

Plasmacytoid Dendritic Cells Are Largely Dispensable for the Pathogenesis of Experimental Inflammatory Bowel Disease.

Front Immunol 2018 25;9:2475. Epub 2018 Oct 25.

Department of Pathology, New York University School of Medicine, New York, NY, United States.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. Read More

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October 2018
3 Reads

Muscarinic m2 receptor-mediated actin polymerization via PI3 kinase γ and integrin-linked kinase in gastric smooth muscle.

Neurogastroenterol Motil 2018 Nov 4:e13495. Epub 2018 Nov 4.

Department of Physiology and Biophysics, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University, Richmond, Virginia.

Background: Actin polymerization plays an important role in smooth muscle contraction. Integrin-linked kinase (ILK) was shown to mediate actin polymerization in airway smooth muscle. The role of ILK in actin polymerization in response to m2 receptor activation was not in gastric smooth muscle. Read More

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November 2018
4 Reads

Wiskott-Aldrich syndrome gene mutations modulate cancer susceptibility in the p53 murine model.

Oncoimmunology 2018 30;7(9):e1468954. Epub 2018 Jul 30.

Department of Microbiology Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.

The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton in hematopoietic cells and mutated in two severe immunodeficiency diseases with high incidence of cancer. Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in WASp and most frequently associated with lymphoreticular tumors of poor prognosis. X-linked neuropenia (XLN) is caused by gain-of-function mutations in WASp and associated with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Read More

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July 2018
4 Reads

Inhibition of profibrotic microRNA-21 affects platelets and their releasate.

JCI Insight 2018 Nov 2;3(21). Epub 2018 Nov 2.

King's British Heart Foundation Centre, King's College London, London, United Kingdom.

Fibrosis is a major contributor to organ disease for which no specific therapy is available. MicroRNA-21 (miR-21) has been implicated in the fibrogenetic response, and inhibitors of miR-21 are currently undergoing clinical trials. Here, we explore how miR-21 inhibition may attenuate fibrosis using a proteomics approach. Read More

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November 2018
5 Reads

Cyclic manner of neutropenia in a patient with HAX-1 mutation.

Pediatr Hematol Oncol 2018 Oct 22:1-5. Epub 2018 Oct 22.

a Department of Pediatric Allergy and Immunology , Kanuni Sultan Suleyman Education and Research Hospital , Istanbul , Turkey.

Introduction: Severe congenital neutropenia (SCN) includes a group of genetic disorders which cause to arrest of neutrophil maturation. SCN can be associated with heterogenous group of genetic defects in ELANE, GFI1, HAX1, G6PC3, JAGN1, VPS45 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene.

Aim: Here we report a patient who has a HAX1 mutation presented with cyclic manner. Read More

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October 2018
1 Read

Advances in site-specific gene editing for primary immune deficiencies.

Authors:
Caroline Y Kuo

Curr Opin Allergy Clin Immunol 2018 Dec;18(6):453-458

Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.

Purpose Of Review: Conventional gene therapy has been a successful, curative treatment modality for many primary immune deficiencies with significant improvements in the last decade. However, the risk of leukemic transformation with viral-mediated gene addition still remains, and unregulated gene addition is not an option for certain diseases in which the target gene is closely controlled. The recent bloom in genome modification platforms has created the opportunity to site-specifically correct mutated DNA base pairs or insert a corrective cDNA minigene while maintaining gene expression under control of endogenous regulatory elements. Read More

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December 2018
19 Reads

High Rates of Community and Hospital Acquired Infections in Patients with Cellular Immunodeficiencies.

J Clin Immunol 2018 Oct 29;38(7):804-809. Epub 2018 Sep 29.

Division of Infectious Diseases, Children's National Health System, Washington, DC, 20010, USA.

Purpose: Patients with primary immunodeficiency diseases (PID) are perceived to be at high risk for acquiring as well as developing complications from infections. There is little data describing the infection type and frequency these patients may acquire in the community or during hospital admissions. Data is critically needed in order to inform best practices on how to protect these vulnerable patients. Read More

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October 2018
4 Reads

Hyper IgE syndromes: clinical and molecular characteristics.

Immunol Cell Biol 2018 Sep 28. Epub 2018 Sep 28.

Seattle Children's Research Institute, Seattle, Washington, USA.

Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels. Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders. However, several other genetically characterized immunodeficiency disorders have been identified over the past decade and joined the umbrella of hyper IgE syndromes including autosomal recessive mutations in the DOCK8, ZNF431 and PGM3 genes and heterozygous mutations with dominant negative effect in the CARD11 gene. Read More

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September 2018
2 Reads

Psychosocial services for primary immunodeficiency disorder families during hematopoietic cell transplantation: A descriptive study.

Palliat Support Care 2018 Sep 18:1-6. Epub 2018 Sep 18.

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

Objective: Caregivers for patients undergoing hematopoietic cell transplantation (HCT) are susceptible to significant psychosocial distress. This cross-sectional study aimed to describe psychosocial support services offered and used by caregivers of pediatric primary immune deficiency (PID) during HCT at 35 hospitals across North America.

Method: Caregivers of pediatric patients with PID were recruited by e-mail to participate in an anonymous 140-question survey instrument between April and May 2016 (N = 171). Read More

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September 2018

Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Disorders: Experience from a Referral Center in India.

Indian Pediatr 2018 Aug;55(8):661-664

Department of Pediatric Haematology, Oncology, Blood and Marrow Transplantation, Apollo Cancer Institutes, Chennai, India.

Objective: To share experience of over 15 years in hematopoietic stem cell transplantation in children with primary immunodeficiency disorders.

Design: Medical record review.

Setting: A referral center for pediatric hemato-oncological disorders. Read More

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August 2018
1 Read

Novel cytoskeletal mutations with immunodeficiency: Why is the raven like a writing desk?

J Allergy Clin Immunol 2018 Nov 4;142(5):1444-1446. Epub 2018 Sep 4.

Rare Diseases Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address:

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November 2018
2 Reads

Experimental Models for Studying Food Allergy.

Cell Mol Gastroenterol Hepatol 2018 7;6(3):356-369.e1. Epub 2018 Jun 7.

Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Immunoglobulin E-mediated food allergy is rapidly developing into a global health problem. Publicly available therapeutic intervention strategies are currently restricted to allergen avoidance and emergency treatments. To gain a better understanding of the disease pathophysiology so that new therapies can be developed, major research efforts have been put into studying food allergy in mice. Read More

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June 2018
4 Reads

Allogeneic Hematopoietic Cell Transplantation in Patients with Primary Immunodeficiencies in Korea: Eleven-Year Experience in a Single Center.

J Clin Immunol 2018 Oct 27;38(7):757-766. Epub 2018 Aug 27.

Division of Hematology and Oncology, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Purpose: We aimed to report our single-center experience of allogeneic hematopoietic cell transplantation (HCT), which has been the only curative option for certain patients with lethal primary immunodeficiencies (PIDs).

Methods: We summarized the results of HCT performed for patients with PIDs for 11 consecutive years from 2006 to 2016 at Samsung Medical Center, Seoul, Korea. Twenty-six patients with PIDs received HCT. Read More

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October 2018
15 Reads

Conformational changes in Arp2/3 complex induced by ATP, WASp-VCA, and actin filaments.

Proc Natl Acad Sci U S A 2018 09 27;115(37):E8642-E8651. Epub 2018 Aug 27.

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;

We used fluorescence spectroscopy and EM to determine how binding of ATP, nucleation-promoting factors, actin monomers, and actin filaments changes the conformation of Arp2/3 complex during the process that nucleates an actin filament branch. We mutated subunits of Arp2/3 complex for labeling with fluorescent dyes at either the C termini of Arp2 and Arp3 or ArpC1 and ArpC3. We measured Förster resonance energy transfer (FRET) efficiency (ET) between the dyes in the presence of the various ligands. Read More

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September 2018
11 Reads

Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive.

J Clin Invest 2018 Aug 20;128(9):4115-4131. Epub 2018 Aug 20.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand the pathophysiology in XLN and the role of WASp in neutrophils, we here examined XLN patients and 2 XLN mouse models. Read More

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August 2018
10 Reads

Bond swapping from a charge cloud allows flexible coordination of upstream signals through WASP: Multiple regulatory roles for the WASP basic region.

J Biol Chem 2018 Sep 13;293(39):15136-15151. Epub 2018 Aug 13.

From the Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom

Wiskott-Aldrich syndrome protein (WASP) activates the actin-related protein 2/3 homolog (Arp2/3) complex and regulates actin polymerization in a physiological setting. Cell division cycle 42 (Cdc42) is a key activator of WASP, which binds Cdc42 through a Cdc42/Rac-interactive binding (CRIB)-containing region that defines a subset of Cdc42 effectors. Here, using site-directed mutagenesis and binding affinity determination and kinetic assays, we report the results of an investigation into the energetic contributions of individual WASP residues to both the Cdc42-WASP binding interface and the kinetics of complex formation. Read More

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September 2018
12 Reads

Surgical Resection Of Thoracic Aortic Aneurysms In Wiskott-Aldrich Syndrome.

Heart Surg Forum 2018 07 2;21(4):E305-E306. Epub 2018 Jul 2.

Department of Cardiovascular Surgery, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey.

Aortic aneurysms are a rare condition in children. Wiskott-Aldrich syndrome is a primary immunodeficiency characterized by infections, thrombocytopenia, and eczema. Aortitis and aneurysm formation seem to be progressive in patients with Wiskott-Aldrich syndrome. Read More

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July 2018
10 Reads

Expression of N471D strumpellin leads to defects in the endolysosomal system.

Dis Model Mech 2018 09 13;11(9). Epub 2018 Sep 13.

Center for Biochemistry, Institute of Biochemistry I, Medical Faculty, University of Cologne, 50931 Cologne, Germany

Hereditary spastic paraplegias (HSPs) are genetically diverse and clinically characterised by lower limb weakness and spasticity. The N471D and several other point mutations of human strumpellin (Str; also known as WASHC5), a member of the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex, have been shown to cause a form of HSP known as spastic paraplegia 8 (SPG8). To investigate the molecular functions of wild-type (WT) and N417D Str, we generated Str cells and ectopically expressed Str-GFP or Str-GFP in Str and WT cells. Read More

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September 2018
2 Reads
4.970 Impact Factor

One hundred percent survival after transplantation of 34 patients with Wiskott-Aldrich syndrome over 20 years.

J Allergy Clin Immunol 2018 Nov 25;142(5):1654-1656.e7. Epub 2018 Jul 25.

Blood and Marrow Transplant Unit, Great Ormond Street Hospital NHS Trust, University College London, London, United Kingdom.

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November 2018
2 Reads
11.480 Impact Factor

Bleeding and splenectomy in Wiskott-Aldrich syndrome: A single-centre experience.

J Allergy Clin Immunol Pract 2018 Jul 23. Epub 2018 Jul 23.

Department of Immunology, Royal Free London NHS Foundation Trust, London, United Kingdom; University College London, Institute of Immunity and Transplantation, London, United Kingdom.

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July 2018
3 Reads

WIPF1 antagonizes the tumor suppressive effect of miR-141/200c and is associated with poor survival in patients with PDAC.

J Exp Clin Cancer Res 2018 Jul 24;37(1):167. Epub 2018 Jul 24.

Department of General Surgery, Fujian Medical University Union Hospital, No.29 Xinquan Road, Fuzhou, 350001, People's Republic of China.

Background: Aberrant expression of Wiskott-Aldrich syndrome protein interacting protein family member 1 (WIPF1) contributes to the invasion and metastasis of several malignancies. However, the role of WIPF1 in human pancreatic ductal adenocarcinoma (PDAC) remains poorly understood.

Methods: Human pancreatic cancer samples from PDAC patients were collected for methylation analysis. Read More

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July 2018
9 Reads

A novel splice site mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report.

BMC Med Genet 2018 Jul 20;19(1):123. Epub 2018 Jul 20.

Persian Bayan Gene Research and Training Institute, Faghihi Medical Genetics Center, Shiraz, Iran.

Background: Wiskott-Aldrich syndrome is an X-linked recessive immunodeficiency due to mutations in Wiskott-Aldrich syndrome (WAS) gene. WAS gene is encoded for a multifunctional protein with key roles in actin polymerization, signaling pathways, and cytoskeletal rearrangement. Therefore, the impaired protein or its absence cause phenotypic spectrum of the disease. Read More

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July 2018
10 Reads

The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses.

Cell Rep 2018 Jul;24(3):619-629

Lymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UK; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.

Wiskott-Aldrich syndrome protein (WASp) is a main cytoskeletal regulator in B cells. WASp-interacting protein (WIP) binds to and stabilizes WASp but also interacts with actin. Using mice with a mutated actin binding domain of WIP (WIPΔABD), we here investigated the role of WIP binding to actin during B cell activation. Read More

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July 2018
2 Reads

Pregnancy, child bearing and prevention of giving birth to the affected children in patients with primary immunodeficiency disease; a case-series.

BMC Pregnancy Childbirth 2018 Jul 11;18(1):299. Epub 2018 Jul 11.

Department of Pediatric, Children's Hospital, University Hospital, LMU, Munich, Germany.

Background: Patients with primary immunodeficiency disease (PID) who survive to adulthood and willing to have a child mostly are worried whether their disease affects their fertility and/or pregnancy and also if their child would be predisposed to PID.

Case Presentation: We report the outcome of conception, pregnancy and their management in 9 families with definite diagnosis of PID. A chronic granulomatous disease subject with an uneventful pregnancy developed fungal sacral osteomyelitis few weeks after delivery. Read More

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July 2018
4 Reads

A novel mutation in Wiskott-Aldrich gene manifesting as macrothrombocytopenia and neutropenia.

BMJ Case Rep 2018 Jul 10;2018. Epub 2018 Jul 10.

Department of Hematology-Oncology, Allegheny General Hospital-Western Pennsylvania Hospital Medical Education Consortium, Pittsburgh, Pennsylvania, USA.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder, described as a clinical triad of microthrombocytopenia, eczema and recurrent infections. Different mutations in WAS gene have been identified, resulting in various phenotypes and a broad range of disease severity, ranging from classic WAS to X-linked thrombocytopenia and X-linked neutropenia. WAS in some cases can be fatal without haematopoietic stem cell transplantation early in life. Read More

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July 2018
5 Reads

A Novel Mutation In A Child With Atypical Wiskott-Aldrich Syndrome Complicated by Cytomegalovirus Infection.

Turk J Haematol 2018 Jul 2. Epub 2018 Jul 2.

Ankara University Medical Faculty, Department of Forensic Medicine Forensic Genetics Laboratory, Ankara, Turkey.

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July 2018
4 Reads

Mapping Active Gene-Regulatory Regions in Human Repopulating Long-Term HSCs.

Cell Stem Cell 2018 Jul;23(1):132-146.e9

Department of Translational and Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Translational Medical Oncology, NCT-Dresden, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Dresden and DKFZ, Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address:

Genes that regulate hematopoietic stem cell (HSC) self-renewal, proliferation, and differentiation are tightly controlled by regulatory regions. However, mapping such regions relies on surface markers and immunophenotypic definition of HSCs. Here, we use γ-retroviral integration sites (γRV ISs) from a gene therapy trial for 10 patients with Wiskott-Aldrich syndrome to mark active enhancers and promoters in functionally defined long-term repopulating HSCs. Read More

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July 2018
13 Reads

A 2-Year-Old Boy With Difficulty Waking After Bone Marrow Transplantation.

Semin Pediatr Neurol 2018 07 1;26:120-123. Epub 2017 Apr 1.

From the Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

We report a 2-year-old boy who was evaluated for difficult waking during prolonged intensive care unit admission associated with bone marrow transplant for Wiskott-Aldrich syndrome. Neurologic examination was found to be abnormal, with nuchal rigidity initially, then decreased extremity movement and areflexia developing over several days. Electromyogram showed length-dependent, axonal, sensorimotor polyneuropathy. Read More

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July 2018
2 Reads

WIP/ITSN1 complex is involved in cellular vesicle trafficking and formation of filopodia-like protrusions.

Gene 2018 Oct 27;674:49-56. Epub 2018 Jun 27.

Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, Kyiv 03680, Ukraine.

WIP (WASP interacting protein) together with N-WASP (neural Wiskott-Aldrich syndrome protein) regulates actin polymerization that is crucial for invadopodia and filopodia formation. Recently, we reported the WIP interaction with ITSN1 which is highly implicated in endo-/exocytosis, apoptosis, mitogenic signaling and cytoskeleton rearrangements. Here we demonstrate that the WIP/ITSN1 complex is involved in the transferrin receptor recycling and partially co-localizes with a marker of the fast recycling endosomes, RAB4. Read More

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October 2018
7 Reads

Thrombopoietin receptor agonists in hereditary thrombocytopenias.

J Thromb Haemost 2018 Sep 27;16(9):1700-1710. Epub 2018 Jul 27.

Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy.

Hereditary thrombocytopenias (HTPs) constitute a heterogeneous group of diseases characterized by a reduction in platelet count and a potential bleeding risk. As a result of advances in diagnostic methods, HTPs are increasingly being identified, and appear to be less rare than previously thought. Most HTPs do not have effective treatments, except for platelet transfusion when bleeding occurs and in preparation for procedures associated with a risk of bleeding. Read More

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September 2018
10 Reads

Newborn screening using TREC/KREC assay for severe T and B cell lymphopenia in Iran.

Scand J Immunol 2018 Jun 26:e12699. Epub 2018 Jun 26.

Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs) are recently used for detection of T or B cell lymphopenia in neonates based on region-specific cutoff levels. Here, we report cutoffs for TREC and KREC copies useful for newborn screening and/or diagnosis of primary immunodeficiency diseases (PID) in Iran. DNA was extracted from a single 3. Read More

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June 2018
5 Reads

IgA Nephropathy Complicated with X-linked Thrombocytopenia.

Acta Med Okayama 2018 Jun;72(3):301-307

Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.

Renal involvement is occasionally observed in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). It has been reported that galactose-deficient IgA is a closely linked to IgA nephropathy (IgAN), suggesting that patients with XLT/WAS associated with reduced galactosylation on serum IgA are susceptible to IgAN. It is necessary to pay more attention to patients with IgAN due to the potential complication with XLT/WAS. Read More

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June 2018
2 Reads

The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.

Nat Commun 2018 06 18;9(1):2377. Epub 2018 Jun 18.

Office of the Dean and the Cancer Center, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX, 78229, USA.

The transition of hematopoiesis from the fetal liver (FL) to the bone marrow (BM) is incompletely characterized. We demonstrate that the Wiskott-Aldrich syndrome verprolin-homologous protein (WAVE) complex 2 is required for this transition, as complex degradation via deletion of its scaffold Hem-1 causes the premature exhaustion of neonatal BM hematopoietic stem cells (HSCs). This exhaustion of BM HSC is due to the failure of BM engraftment of Hem-1 FL HSCs, causing early death. Read More

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June 2018
4 Reads
10.740 Impact Factor

Alpha protocadherins and Pyk2 kinase regulate cortical neuron migration and cytoskeletal dynamics via Rac1 GTPase and WAVE complex in mice.

Elife 2018 Jun 18;7. Epub 2018 Jun 18.

Key Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Diverse clustered protocadherins are thought to function in neurite morphogenesis and neuronal connectivity in the brain. Here, we report that the protocadherin alpha () gene cluster regulates neuronal migration during cortical development and cytoskeletal dynamics in primary cortical culture through the WAVE (Wiskott-Aldrich syndrome family verprolin homologous protein, also known as Wasf) complex. In addition, overexpression of proline-rich tyrosine kinase 2 (Pyk2, also known as Ptk2b, Cakβ, Raftk, Fak2, and Cadtk), a non-receptor cell-adhesion kinase and scaffold protein downstream of Pcdhα, impairs cortical neuron migration via inactivation of the small GTPase Rac1. Read More

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June 2018
25 Reads

WAVE3 promotes proliferation, migration and invasion via the AKT pathway in pancreatic cancer.

Int J Oncol 2018 Aug 25;53(2):672-684. Epub 2018 May 25.

Department of Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.

Alterations in Wiskott-Aldrich syndrome protein family verprolin-homologous protein 3 (WAVE3) expression play various roles in certain types of cancer. However, the roles of WAVE3 expression in pancreatic cancer remain unknown. The present retrospective study demonstrated that WAVE3 expression was higher in cancerous pancreatic tissues than in non-neoplastic tissues. Read More

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August 2018
29 Reads

[N-WASP regulates cortical neuron migration through its polyPro and VCA domains].

Yi Chuan 2018 May;40(5):390-401

Key Laboratory of Systems Biomedicine (Ministry of Education), Center for Comparative Biomedicine, Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.

Cortical neuron migration in the developing mouse forebrain is a complex process, which contains several steps related to cytoskeleton dynamics and remodeling. Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP-WAVE family, regulates actin cytoskeleton reorganization through the binding of its VCA domain to the Arp2/3 complex. Here we report expression patterns of N-WASP gene in the mouse developing embryonic cortex (E12. Read More

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May 2018
2 Reads

Discovering the Cause of Wiskott-Aldrich Syndrome and Laying the Foundation for Understanding Immune Cell Structuring.

J Immunol 2018 Jun;200(11):3667-3670

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030; and Center for Human Immunobiology, Texas Children's Hospital, Houston, TX 77030

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June 2018
2 Reads

Autoimmune thyroiditis following HLA-matched sibling hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome.

Pediatr Transplant 2018 08 15;22(5):e13222. Epub 2018 May 15.

Division of Pediatric Hematology Oncology, Children's Hospital of Michigan, Detroit, MI, USA.

WAS is a fatal X-linked combined immunodeficiency syndrome, the only cures for which are HSCT or gene therapy. AID occur in up to 72% of patients with WAS who do not receive HSCT, likely arising secondary to impaired multilineage immune autoregulatory function; AITD is not typically seen. In this article, we describe the case of a male patient who underwent HLA-matched HSCT for WAS at the age of 5 months, with his sister (a WAS carrier) acting as his donor and subsequently developed AITD 12 months post-transplant, with marked elevation of antithyroid peroxidase antibody titer. Read More

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August 2018
4 Reads

Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson's disease.

Proc Natl Acad Sci U S A 2018 05 14;115(22):E5164-E5173. Epub 2018 May 14.

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada;

Leucine-rich repeat kinase 2 () has been implicated in both familial and sporadic Parkinson's disease (PD), yet its pathogenic role remains unclear. A previous screen in identified Scar/WAVE (Wiskott-Aldrich syndrome protein-family verproline) proteins as potential genetic interactors of Here, we provide evidence that LRRK2 modulates the phagocytic response of myeloid cells via specific modulation of the actin-cytoskeletal regulator, WAVE2. We demonstrate that macrophages and microglia from PD patients and mice display a WAVE2-mediated increase in phagocytic response, respectively. Read More

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May 2018
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High PINCH1 Expression in Human Laryngeal Carcinoma Associates with Poor Prognosis.

Anal Cell Pathol (Amst) 2018 20;2018:2989635. Epub 2018 Mar 20.

Department of Anatomy, Medical School of Patras, 26504 Patras, Greece.

Focal adhesion signaling to actin cytoskeleton is critically implicated in cell migration and cancer invasion and metastasis. Actin-binding proteins cofilin and N-WASP regulate actin filament turnover, and focal adhesion proteins parvins and PINCH mediate integrin signaling to the actin cytoskeleton. Altered expression of these proteins has been implicated in human cancer. Read More

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October 2018
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