Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome

WOS: 000287894600008PubMed ID: 21185603The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. WAS is caused by mutations in the WASP gene which encodes WASP, a 502-amino acid protein. WASP plays a critical role in actin cytoskeleton organization and signalling, and functions of immune cells. We present here the results of genetic analysis of patients with WAS from eleven Eastern and Central European (ECE) countries and Turkey. Clinical and haematological information of 87 affected males and 48 carrier females from 77 WAS families were collected. The WASP gene was sequenced from genomic DNA of patients with WAS, as well as their family members to identify carriers. In this large cohort, we identified 62 unique mutations including 17 novel sequence variants. The mutations were scattered throughout the WASP gene and included single base pair changes (17 missense and 11 nonsense mutations), 7 small insertions, 18 deletions, and 9 splice site defects. Genetic counselling and prenatal diagnosis were applied in four affected families. This study was part of the J Project aimed at identifying genetic basis of primary immunodeficiency disease in ECE countries. This report provides the first comprehensive overview of the molecular genetic and demographic features of WAS in ECE. (C) 2010 Elsevier Ltd. All rights reserved.Hungarian Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA PD 72445]; European Social FundEuropean Social Fund (ESF) [4.2.1./B-09/1/KONV-2010-0007]We thank Drs. LD Notarangelo, J van Dongen, C Klein, A Jones, M Losekoot, E Remold-O'Donell, K Schwartz, and H Ochs for their help in analysing some of our patients and supporting molecular diagnostic work in their labs. We thank the Jeffrey Modell Foundation for their support of several laboratories to perform molecular genetic testing. This work was supported by grants from the Hungarian Research Fund (OTKA PD 72445) to ME, and the TAMOP 4.2.1./B-09/1/KONV-2010-0007 project implemented through the New Hungary Development Plan and co-financed by the European Social Fund

NOVEL AND RECURRENT WASP MUTATIONS IN EASTERN AND CENTRAL EUROPEAN PATIENTS WITH WAS

100th J Project Meeting -- MAR 12-14, 2014 -- Antalya, TURKEYWOS: 000341839800046E Cent European Infect & Pediat Immunol Ctr Training & Re