title: Detection of 28 novel mutations in the Wiskott-Aldrich syndrome and X-linked thrombocytopenia based on multiplex PCR.
abstract: The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder including microthrombocytopenia, eczema and immunodeficiency. A mild form is known as the X-linked thrombocytopenia (XLT). We screened 150 individuals or families based on a multiplex PCR method. We found 28 novel mutations (7 missense, 1 nonsense, 1 nonstop change, 5 splice site mutations and 14 deletions or insertions). The method relied on the co-synthesis of 5 amplicons and direct sequencing, optimizing the novel protocol proposed by Jones et al. [L.N. Jones, M.I. Lutskiy, J. Cooley, et al. A novel protocol to identify mutations in patients with Wiskott-Aldrich syndrome, Blood Cells Mol. Dis. 28 (2002) 392-398]. It was thus possible to identify faster and at a lower cost the mutations in newly diagnosed patients. The mutation distribution, according to the type, was in keeping with the distribution reported previously. No clear-cut genotype-phenotype correlation was observed.
authors.affiliation: Service d'Hématologie, d'Immunologie et de Cytogénétique, Hôpital de Bicêtre, AP-HP, 78 rue du Général-Leclerc, 94275, Le Kremlin-Bicêtre, France. hematobct.sequence@bct.aphp.fr
authors.forename: Alexis
authors.initials: A
authors.lastname: Proust
authors.forename: Benoît
authors.initials: B
authors.lastname: Guillet
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint Basile
authors.forename: Corinne
authors.initials: C
authors.lastname: Pondarré
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.forename: Marie
authors.initials: M
authors.lastname: Dreyfus
authors.forename: Gil
authors.initials: G
authors.lastname: Tchernia
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Jean
authors.initials: J
authors.lastname: Delaunay
mesh_terms: D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005602:France; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D013921:Thrombocytopenia / Q000175:diagnosis / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000175:diagnosis / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*
chemical_list: C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein