title: Genetic characteristics of eighty-seven patients with the Wiskott-Aldrich syndrome.
abstract: 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.
authors.affiliation: Department of Infectious and Pediatric Immunology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
authors.forename: Vera
authors.initials: V
authors.lastname: Gulácsy
authors.forename: Tomas
authors.initials: T
authors.lastname: Freiberger
authors.forename: Anna
authors.initials: A
authors.lastname: Shcherbina
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pac
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Chernyshova
authors.forename: Tadej
authors.initials: T
authors.lastname: Avcin
authors.forename: Irina
authors.initials: I
authors.lastname: Kondratenko
authors.forename: Larysa
authors.initials: L
authors.lastname: Kostyuchenko
authors.forename: Tatjana
authors.initials: T
authors.lastname: Prokofjeva
authors.forename: Srdjan
authors.initials: S
authors.lastname: Pasic
authors.forename: Ewa
authors.initials: E
authors.lastname: Bernatowska
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.forename: Jelena
authors.initials: J
authors.lastname: Rascon
authors.forename: Nicolae
authors.initials: N
authors.lastname: Iagaru
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mazza
authors.forename: Beáta
authors.initials: B
authors.lastname: Tóth
authors.forename: Melinda
authors.initials: M
authors.lastname: Erdos
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.forename: László
authors.initials: L
authors.lastname: Maródi
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D051316:Wiskott-Aldrich Syndrome Protein