A novel large deletion and single nucleotide insertion in the Wiskott–Aldrich syndrome protein gene

Gulácsy, Vera; Soltész, Beáta; Petrescu, Cristina; Bătăneanţ, Mihaela; Gyimesi, Edit; Şerban, M.; Maródi, László; Töth, Beáta

doi:10.1111/ejh.12424

Cited by 4 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To coordinate the activity of the JP, the JP Steering Committee (SC) was established in 2010; following this year SC meetings were regularly organized mostly in Budapest, Hungary, or at the time of ESID congresses (Edinburgh and Lisbon in 2017 and 2018, respectively) ( Supplementary Figure 1 ). These SC meetings outlined previous achievements and future programs of the JP including joint clinical research which were published in reasonable international journals ( 28 – 33 ). An SC meeting to remember was the one in March 2019.…”

Section: Resultsmentioning

confidence: 99%

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

et al. 2022

Self Cite

View full text Add to dashboard Cite

IntroductionThe J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.

show abstract

Section: Resultsmentioning

confidence: 99%

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…We report this mutation for the first time, and it is also the first time to verify that this mutation decreased the expression of WASP and provided more evidence supporting the pathogenicity of the mutation [ 23 ]. Researching and reporting novel pathogenic mutations in the WAS gene will broaden the spectrum of mutations associated with this gene, facilitating genetic counseling and prenatal diagnosis [ 24 ]. This study has expanded the gene mutation database of WAS syndrome and has offered new insights for more accurate identification of mutation types and clinical treatment of XLT patients.…”

Section: Discussionmentioning

confidence: 99%

A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family

Wang,

Zhang,

et al. 2024

International Journal of Genomics

View full text Add to dashboard Cite

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disease characterized by clinical symptoms such as eczema, thrombocytopenia with small platelets, immune deficiency, prone to autoimmune diseases, and malignant tumors. This disease is caused by mutations of the WAS gene encoding WASprotein (WASP). The locus and type of mutations of the WAS gene and the expression quantity of WASP were strongly correlated with the clinical manifestations of patients. We found a novel mutation in the WAS gene (c.931+5G>C), which affected splicing to produce three abnormal mRNA, resulting in an abnormally truncated WASP. This mutation led to a reduction but not the elimination of the normal WASP population, resulting in causes X-linked thrombocytopenia (XLT) with mild clinical manifestations. Our findings revealed the pathogenic mechanism of this mutation.

show abstract

“…Altogether, genetic analysis in these three institutions was performed on 316 samples submitted from patients from 15 JP countries (Table 2). Part of the results of these studies has been published before 3,12‐20 …”

Section: Figurementioning

confidence: 99%

“…Part of the results of these studies has been published before. 3,[12][13][14][15][16][17][18][19][20] Taken together, these data suggest that the contribution of the JP to better care of patients and the advancement of clinical research in the field of PID is outstanding and unique in Eurasia over the past two decades.…”

Section: Ta B L E 1 Clinical and Laboratory Data Of Patients With Slc...mentioning

confidence: 99%

A novel mutation in SLC39A7 identified in a patient with autosomal recessive agammaglobulinemia: The impact of the J Project

Erdős

Mironska

Kareva

et al. 2022

Pediatric Allergy Immunology

Self Cite

View full text Add to dashboard Cite

To the Editor, ZIP7 deficiency is the most recently described congenital agammaglobulinemia with autosomal recessive inheritance. 1 ZIP7, encoded by SLC39A7, is an endoplasmic reticulum-to-cytoplasm Zn 2+ transporter. Developing B cells are sensitive to altered Zn 2+ distribution, which causes developmental blockade beyond the pre-B cell stage. 2 Complete loss of ZIP7 in cell lines causes a reduction in cytoplasmic Zn 2+ and an increase in endoplasmic reticulum Zn 2+ concentration. Since the original report in 2019, no additional cases of ZIP7 deficiency have been published. Here, we describe a patient evaluated for recurrent respiratory tract infections, meningitis, agammaglobulinemia, and B cell lymphopenia, ultimately found to carry a novel SLC39A7 variant. We describe his clinical characteristics, immunological findings, and genetic investigations.We also report on the impact of the J Project (JP) in improving primary immunodeficiency (PID) patient care and research in Eastern and Central Europe (ECE).The patient and his family members were interviewed, examined, treated, and monitored at the University Clinic for Children's Disease in Skopje. Medical records were obtained from the electronic registry of the University Clinic. The mother of the patient has given written informed consent to conduct the study and for the publication of data. All procedures were performed in accordance with the ethical standards of the Institutional Research Committee.Genomic DNA from the patient and his family members was isolated with the Gen Elute Blood Genomic DNA kit (Sigma-Aldrich) and subjected to whole-exome sequencing (WES) in the patient and targeted gene sequencing in the patient and available family members. 3 WES was performed at the New York Genome Center and the Rockefeller University using an Illumina HiSeq 2500 sequencing system (Illumina). Exome capture was carried out with SureSelect human all exome kit (Agilent) in accordance with the manufacturer's instructions. Putative disease alleles found by WES were validated by dideoxy Sanger sequencing in the patient AND in family members. Exons and flanking intronic regions of SLC39A7 wereThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

show abstract

A novel large deletion and single nucleotide insertion in the Wiskott–Aldrich syndrome protein gene

Cited by 4 publications

References 24 publications

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021

A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family

A novel mutation in SLC39A7 identified in a patient with autosomal recessive agammaglobulinemia: The impact of the J Project

Contact Info

Product

Resources

About