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A familial case of Wiskott-Aldrich Syndrome with a hotspot mutation in exon 2 of the WAS Gene.

ABSTRACT: The Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder characterized classically by thrombocytopenia, immunodeficiency, and eczema. The phenotype observed in this syndrome is caused by mutation in the WAS gene. Peripheral blood DNAs were isolated from an 18-month-old boy with WAS and his mother, maternal uncle, and maternal grandmother. Genetic analysis for the detection of a mutation of WAS gene was performed by polymerase chain reaction-single strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing of the PCR product. In PCR-SSCP, the patient and his maternal uncle had an abnormal shift band, which was not found in normal controls, and his mother and maternal grandmother showed heterozygous bands. In direct sequencing analysis, the patient with WAS had CGC-->CAC point mutation in exon 2 that resulted in an amino acid change in codon 86 (Arg86His). The present study identified a gene mutation responsible for WAS at a mutation hotspot of the WAS gene in a Korean family.

SUBMITTER: Park SK

PROVIDER: S-EPMC2694638 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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A familial case of Wiskott-Aldrich Syndrome with a hotspot mutation in exon 2 of the WAS Gene.

Park Sook Kyung SK Kim Chun Soo CS Song Dae Kyu DK Kim Joo Young JY Choi In Jang IJ Kim Dae Kwang DK

Journal of Korean medical science 20071201 6

The Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder characterized classically by thrombocytopenia, immunodeficiency, and eczema. The phenotype observed in this syndrome is caused by mutation in the WAS gene. Peripheral blood DNAs were isolated from an 18-month-old boy with WAS and his mother, maternal uncle, and maternal grandmother. Genetic analysis for the detection of a mutation of WAS gene was performed by polymerase chain reaction-single strand conformational polymorphism analy ...[more]

PMID: 18162713

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Project description:ImportanceWiskott-Aldrich syndrome is a rare primary immunodeficiency associated with severe microthrombocytopenia. Partially HLA antigen-matched allogeneic hematopoietic stem cell (HSC) transplantation is often curative but is associated with significant comorbidity.ObjectiveTo assess the outcomes and safety of autologous HSC gene therapy in Wiskott-Aldrich syndrome.Design, setting, and participantsGene-corrected autologous HSCs were infused in 7 consecutive patients with severe Wiskott-Aldrich syndrome lacking HLA antigen-matched related or unrelated HSC donors (age range, 0.8-15.5 years; mean, 7 years) following myeloablative conditioning. Patients were enrolled in France and England and treated between December 2010 and January 2014. Follow-up of patients in this intermediate analysis ranged from 9 to 42 months.InterventionA single infusion of gene-modified CD34+ cells with an advanced lentiviral vector.Main outcomes and measuresPrimary outcomes were improvement at 24 months in eczema, frequency and severity of infections, bleeding tendency, and autoimmunity and reduction in disease-related days of hospitalization. Secondary outcomes were improvement in immunological and hematological characteristics and evidence of safety through vector integration analysis.ResultsSix of the 7 patients were alive at the time of last follow-up (mean and median follow-up, 28 months and 27 months, respectively) and showed sustained clinical benefit. One patient died 7 months after treatment of preexisting drug-resistant herpes virus infection. Eczema and susceptibility to infections resolved in all 6 patients. Autoimmunity improved in 5 of 5 patients. No severe bleeding episodes were recorded after treatment, and at last follow-up, all 6 surviving patients were free of blood product support and thrombopoietic agonists. Hospitalization days were reduced from a median of 25 days during the 2 years before treatment to a median of 0 days during the 2 years after treatment. All 6 surviving patients exhibited high-level, stable engraftment of functionally corrected lymphoid cells. The degree of myeloid cell engraftment and of platelet reconstitution correlated with the dose of gene-corrected cells administered. No evidence of vector-related toxicity was observed clinically or by molecular analysis.Conclusions and relevanceThis study demonstrated the feasibility of the use of gene therapy in patients with Wiskott-Aldrich syndrome. Controlled trials with larger numbers of patients are necessary to assess long-term outcomes and safety.

Dataset Information

A familial case of Wiskott-Aldrich Syndrome with a hotspot mutation in exon 2 of the WAS Gene.

Publications

A familial case of Wiskott-Aldrich Syndrome with a hotspot mutation in exon 2 of the WAS Gene.

Similar Datasets

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