title: Clinical course of patients with WASP gene mutations.
abstract: Mutations of the Wiskott-Aldrich syndrome protein (WASP) gene result either in the classic Wiskott-Aldrich syndrome (WAS) or in a less severe form, X-linked thrombocytopenia (XLT). A phenotype-genotype correlation has been reported by some but not by other investigators. In this study, we characterized WASP gene mutations in 50 Japanese patients and analyzed the clinical phenotype and course of each. All patients with missense mutations were WASP-positive. In contrast, patients with nonsense mutations, large deletions, small deletions, and small insertions were WASP-negative. Patients with splice anomalies were either WASP-positive or WASP-negative. The clinical phenotype of each patient was correlated with the presence or absence of WASP. Lack of WASP expression was associated with susceptibility to bacterial, viral, fungal, and Pneumocystis carinii infections and with severe eczema, intestinal hemorrhage, death from intracranial bleeding, and malignancies. Rates for overall survival and survival without intracranial hemorrhage or other serious complications were significantly lower in WASP-negative patients. This analysis provides evidence for a strong phenotype-genotype correlation and demonstrates that WAS protein expression is a useful tool for predicting long-term prognosis for patients with WAS/XLT. Based on data presented here, hematopoietic stem cell transplantation should be considered, especially for WASP-negative patients, while the patients are young to improve prognosis.
authors.affiliation: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. kimai.ped@tmd.ac.jp
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Imai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yinzhu
authors.initials: Y
authors.lastname: Jin
authors.forename: Sukeyuki
authors.initials: S
authors.lastname: Itoh
authors.forename: Michiko
authors.initials: M
authors.lastname: Kajiwara
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Yata
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D017398:Alternative Splicing; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D018389:Codon, Nonsense; D004251:DNA Transposable Elements / Q000235:genetics; D005091:Exons / Q000235:genetics; D006470:Hemorrhage / Q000453:epidemiology*; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D014923:Wiskott-Aldrich Syndrome / Q000097:blood / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein
chemical_list: D018389:Codon, Nonsense; D004251:DNA Transposable Elements; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein