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

Autor: Glanzmann B; 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., Möller M; 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., Schoeman M; 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., Urban M; 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., van Helden PD; 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., Frigati L; Division of Paediatric Infectious Diseases, Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Grewal R; Division of Haematology, National Health Laboratory Services, Tygerberg Hospital, Cape Town, South Africa., Pieters H; Division of Haematology, National Health Laboratory Services, Tygerberg Hospital, Cape Town, South Africa., Loos B; Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa., Hoal EG; 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., Glashoff RH; Immunology Unit, Division of Medical Microbiology, National Health Laboratory Service and Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa., Cornelissen H; Department of Haematopathology, National Health Laboratory Service and Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa., Rabie H; Division of Paediatric Infectious Diseases, Department of Paediatrics and Child Health, Tygerberg Children's Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Esser MM; Immunology Unit, Division of Medical Microbiology, National Health Laboratory Service and Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa., Kinnear CJ; 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. gkin@sun.ac.za.
Jazyk: angličtina
Zdroj: BMC medical genetics [BMC Med Genet] 2020 Jun 05; Vol. 21 (1), pp. 124. Date of Electronic Publication: 2020 Jun 05.
DOI: 10.1186/s12881-020-01054-6
Abstrakt: 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.
Case Presentation: Here, we describe a three-year-old HIV negative boy presenting with recurrent infections, skin rashes, features of autoimmunity and atopy. However, platelets were initially reported as normal in numbers and morphology as were baseline immune investigations. An older male sibling had died in infancy from suspected immunodeficiency. Uncertainty of diagnosis and suspected severe PIDD prompted urgent further molecular investigation. Whole exome sequencing identified c. 397 G > A as a novel hemizygous missense mutation located in exon 4 of WAS.
Conclusion: With definitive molecular diagnosis, we could target treatment and offer genetic counselling and prenatal diagnostic testing to the family. The identification of novel variants is important to confirm phenotype variations of a syndrome.
Databáze: MEDLINE
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