title: Wiskott-Aldrich syndrome in a girl caused by heterozygous WASP mutation and extremely skewed X-chromosome inactivation: a novel association with maternal uniparental isodisomy 6.
abstract: Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema and immune deficiency, caused primarily by mutations in the WASP (Wiskott-Aldrich syndrome protein) gene. Female carriers are usually asymptomatic because of the preferential activation of the normal, nonmutated X-chromosome in their hematopoietic cells. We report our observations of a female child with WAS, who displayed symptoms of congenital thrombocytopenia. DNA sequencing analysis of the WASP gene revealed a heterozygous nonsense mutation in exon 10. The expressions of WASP and normal WASP mRNA were defective. We found preferential inactivation of the X-chromosome on which wild-type WASP was located. Single-nucleotide polymorphism microarray testing and the analysis of the polymorphic variable number of tandem repeat regions revealed maternal uniparental isodisomy of chromosome 6 (UPD6). Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation.
authors: Departments of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Tomohito
authors: T
authors: Takimoto
authors: Hidetoshi
authors: H
authors: Takada
authors: Masataka
authors: M
authors: Ishimura
authors: Makiko
authors: M
authors: Kirino
authors: Kenichiro
authors: K
authors: Hata
authors: Osamu
authors: O
authors: Ohara
authors: Tomohiro
authors: T
authors: Morio
authors: Toshiro
authors: T
authors: Hara
mesh_terms: D041321:Chromosomes, Human, X / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D017384:Sequence Deletion; D024182:Uniparental Disomy / Q000235:genetics*; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein