scholarly journals The phenomenon of reverse mutation in a patient with Wiskott–Aldrich syndrome

2019 ◽  
Vol 18 (3) ◽  
pp. 104-111 ◽  
Author(s):  
Z. A. Nesterenko ◽  
N. B. Kuzmenko ◽  
V. I. Burlakov ◽  
E. A. Victorova ◽  
V. A. Vedmedskaya ◽  
...  
Keyword(s):  
Immune System ◽  
Phenotypic Diversity ◽  
Somatic Mosaicism ◽  
Mild Form ◽  
Reverse Mutation ◽  
Wiskott Aldrich Syndrome ◽  
Appropriate Treatment ◽  
Delay Of Diagnosis ◽  
Was Gene ◽  
Genetic Phenomenon

Primary immunodeficiencies (PIDS) are genetically caused heterogeneous diseases of the immune system. One of the genetic phenomenon affecting the phenotypic diversity of PIDS is a reverse somatic mosaicism (RM) observed in different groups of PIDS. The majority of RM cases are described in patients with Wiskott–Aldrich syndrome (WAS). Despite the fact that PM does not always lead to a mild form of the disease, the presence of this phenomenon can cause the delay of diagnosis and start of the appropriate treatment. This article presents the case of a patient with Wiskott–Aldrich syndrome with a reverse mutation in the WAS gene. Parents gave their consent to use information about the child in the article.

A novel mutation of the WAS gene in a patient with Wiskott-Aldrich syndrome presenting with recalcitrant viral warts

2010 ◽  
Vol 60 (2) ◽  
pp. 120-122 ◽  
Author(s):  
Jin Ki Kim ◽  
Moon Soo Yoon ◽  
Ji Young Huh ◽  
Hee-Jin Kim ◽  
Dong Hyun Kim
Keyword(s):  
Novel Mutation ◽  
Wiskott Aldrich Syndrome ◽  
Was Gene

scholarly journals The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3797-3804 ◽  
Author(s):  
Q Zhu ◽  
M Zhang ◽  
RM Blaese ◽  
JM Derry ◽  
A Junker ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Point Mutations ◽  
Gene Mutations ◽  
Exon Skipping ◽  
Splice Site Mutation ◽  
Missense Mutations ◽  
Site Mutation ◽  
Exon 2 ◽  
Wiskott Aldrich Syndrome ◽  
Was Gene

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, small platelets, eczema, recurrent infections, and immunodeficiency. Besides the classic WAS phenotype, there is a group of patients with congenital X-linked thrombocytopenia (XLT) who have small platelets but only transient eczema, if any, and minimal immune deficiency. Because the gene responsible for WAS has been sequenced, it was possible to correlate the WAS phenotypes with WAS gene mutations. Using a fingerprinting screening technique, we determined the approximate location of the mutation in 13 unrelated WAS patients with mild to severe clinical symptoms. Direct sequence analysis of cDNA and genomic DNA obtained from patient-derived cell lines showed 12 unique mutations distributed throughout the WAS gene, including insertions, deletions, and point mutations resulting in amino acid substitutions, termination, exon skipping, or splicing defects. Of 4 unrelated patients with the XLT phenotype, 3 had missense mutations affecting exon 2 and 1 had a splice-site mutation affecting exon 9. Patients with classic WAS had more complex mutations, resulting in termination codons, frameshift, and early termination. These findings provide direct evidence that XLT and WAS are caused by mutations of the same gene and suggest that severe clinical phenotypes are associated with complex mutations.

scholarly journals Wiskott-Aldrich syndrome: report of an autosomal dominant variant

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4538-4543 ◽  
Author(s):  
B Rocca ◽  
A Bellacosa ◽  
R De Cristofaro ◽  
G Neri ◽  
M Della Ventura ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Autosomal Gene ◽  
Chromosome 16 ◽  
Chromosome X ◽  
Autosomal Dominant Trait ◽  
Giant Platelets ◽  
Wiskott Aldrich Syndrome ◽  
Structural Abnormalities ◽  
Clinical Triad ◽  
Was Gene

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder originally described as a clinical triad of thrombocytopenia with small platelets, eczema, and immunodeficiency. Impaired CD43 glycoprotein expression on lymphocytes is a typical hallmark of this disorder. The CD43 gene is located on chromosome 16, and the WAS gene, WASP, was recently isolated from the chromosome X p11.22-p11.23. This gene, mutated in WAS patients, encodes a protein that is likely to play a role in controlling the expression of CD43. However, the molecular mechanism(s) causing WAS are not yet known. Herein, we describe a three- generation family in which clinical and laboratory WAS features were expressed in six of nine subjects available for study. At variance with classic X-linked WAS, this disorder was characterized by the presence of thrombocytopenia with a broad spectrum of platelet size, including giant platelets, and was inherited as an autosomal dominant trait. This last finding led us to hypothesize a mutation of the CD43 gene. However, Southern blot analysis failed to detect structural abnormalities of this gene, and genotype analysis ruled out the possibility that a CD43 allele might be shared by the affected individuals. These findings indicate that an alteration(s) of an autosomal gene distinct from the CD43 gene is responsible for the disease. Thus, results from this family, providing the first observation of an autosomally transmitted WAS variant, indicate that genetic mechanism(s) leading to WAS are more complex than previously recognized.

Genome editing: An alternative to retroviral vectors for Wiskott-Aldrich Syndrome (WAS) Gene Therapy?

2016 ◽  
Vol 4 (3) ◽  
pp. 281-289
Author(s):  
F. Martin ◽  
A. Gutierrez-Guerrero ◽  
S. Sánchez ◽  
G. Galvani ◽  
K. Benabdellah
Keyword(s):  
Gene Therapy ◽  
Genome Editing ◽  
Retroviral Vectors ◽  
Wiskott Aldrich Syndrome ◽  
Was Gene

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

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Hossein Esmaeilzadeh ◽  
Mohammad Reza Bordbar ◽  
Hassan Dastsooz ◽  
Mohammad Silawi ◽  
Mohammad Ali Farazi Fard ◽  
...  
Keyword(s):  
Case Report ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Chronic Colitis ◽  
Site Mutation ◽  
Wiskott Aldrich Syndrome ◽  
Was Gene

Evidence for Efficacy and Safety of Lentiviral Mediated Gene Transfer in T Cells and CD34+ Cells from Wiskott-Aldrich Syndrome Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3279-3279
Author(s):  
Samantha Scaramuzza ◽  
Sara Trifari ◽  
Francesco Marangoni ◽  
Silvana Martino ◽  
Ayse Metin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
Gene Transfer ◽  
Lentiviral Vector ◽  
Efficacy And Safety ◽  
Wiskott Aldrich Syndrome ◽  
Cd34 Cells ◽  
Was Gene

Abstract Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency characterized by eczema, recurrent infections, severe hemorrhages and lymphomas. Transplantation of hematopoietic stem cells from HLA-identical sibling donors is a resolutive treatment, but it is available only for a minority of patients. Therapy based on the transplant of genetically correct autologous stem cells could represent a valid alternative approach. We investigated the efficacy and the safety of WAS gene transfer using HIV-based lentiviral vector encoding for WAS cDNA under the control of an autologous promoter (1.6 kb). T cells obtained from WAS patients showed normal level of WAS expression after lentiviral transduction. Transduced T cells showed a correction in TCR-driven proliferation and IL-2 production. Furthermore, a selective growth advantage of transduced T cells was observed in long-term in vitro cultures. Studies in T cell clones generated from transduced WAS CD4+ T cells revealed that 1–2 vector copies were necessary and sufficient to correct T cells function. CD34+ cells, isolated from mobilized peripheral blood and bone marrow of healthy donors, were transduced using WASP or GFP-encoding lentiviral vectors. Cells were cultured in the presence of different cytokines to investigate if WAS gene transfer could have any effect on short and long-term differentiation (CFU-C, LTC-IC and B/NK assays). Transduction resulted in a comparable number of CFU-C and LTC-IC colonies and normal B and NK cells differentiation with respect to untransduced cells. Furthermore, transduction of CD34+ cells isolated from the bone marrow of a WAS patient was performed under optimized culture conditions. Lentiviral gene transfer led to restoration of WASP expression in differentiated cells with copy number ranging from 1 to 5 copies per cell. In conclusion, our data demonstrate that the WAS promoter/cDNA-containing lentiviral vector can efficiently transduce and restore WASP expression in CD34+ cells and T cells from WAS patients. Experiments in the Rag2−/−/γchain- murine model are ongoing to test the efficacy and safety of the WASP transduced CD34+ cells. Together, our studies provide a preclinical basis for the implementation of a gene therapy trial for WAS patients.

A novel splice site mutation in the WAS gene causes Wiskott???Aldrich syndrome in two siblings of a Saudi family

2004 ◽  
Vol 15 (7) ◽  
pp. 599-603
Author(s):  
Khaled K Abu-Amero ◽  
Tarek M Owaidah ◽  
Abduallah Al Jefri ◽  
Abdulaziz Al-Ghonaium ◽  
Ibrahim M Fawaz ◽  
...  
Keyword(s):  
Splice Site ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
Wiskott Aldrich Syndrome ◽  
Saudi Family ◽  
Was Gene

A Novel Mutation W252X in the WAS Gene in a Korean Patient with Wiskott-Aldrich Syndrome

2006 ◽  
Vol 83 (5) ◽  
pp. 426-428 ◽  
Author(s):  
Hee-Jin Kim ◽  
Eun-Hyung Yoo ◽  
Chang-Seok Ki ◽  
Geon-Hee Yoo ◽  
Hong-Hoe Koo ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Korean Patient ◽  
Wiskott Aldrich Syndrome ◽  
Was Gene

scholarly journals Current Clinical and Pre-Clinical Imaging Approaches to Study the Cancer-Associated Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Christopher G. Mueller ◽  
Christian Gaiddon ◽  
Aïna Venkatasamy
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Standard Procedure ◽  
Cellular Level ◽  
Clinical Settings ◽  
Non Invasive ◽  
Technological Advances ◽  
Appropriate Treatment ◽  
Approaches To Study ◽  
Near Future

In the light of the success and the expected growth of its arsenal, immuno-therapy may become the standard neoadjuvant procedure for many cancers in the near future. However, aspects such as the identity, organization and the activation status of the peri- and intra-tumoral immune cells would represent important elements to weigh in the decision for the appropriate treatment. While important progress in non-invasive imaging of immune cells has been made over the last decades, it falls yet short of entering the clinics, let alone becoming a standard procedure. Here, we provide an overview of the different intra-vital imaging approaches in the clinics and in pre-clinical settings and discuss their benefits and drawbacks for assessing the activity of the immune system, globally and on a cellular level. Stimulated by further research, the future is likely to see many technological advances both on signal detection and emission as well as image specificity and resolution to tackle current hurdles. We anticipate that the ability to precisely determine an immune stage of cancer will capture the attention of the oncologist and will create a change in paradigm for cancer therapy.

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