Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome
The 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.
|Keywords||WASP mutation, Wiskott Aldrich syndrome, Wiskott Aldrich syndrome protein, Wiskott-Aldrich syndrome, X chromosome recessive disorder, article, autoimmune disease, clinical feature, cytoskeleton, demography, female, gene amplification, gene deletion, gene insertion, gene mutation, genetic counseling, heterozygote, human, major clinical study, male, missense mutation, nonsense mutation, nucleotide sequence, prenatal diagnosis, priority journal, sequence analysis, thrombocytopenia|
|Persistent URL||dx.doi.org/10.1016/j.molimm.2010.11.013, hdl.handle.net/1765/22867|
Gulácsy, V, Freiberger, T, Shcherbina, A, Pac, M, Chernyshova, I, Avcin, T, … Maródi, L. (2011). Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome. Molecular Immunology, 48(5), 788–792. doi:10.1016/j.molimm.2010.11.013