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

Tomohito Takimoto, Hidetoshi Takada, Masataka Ishimura, Makiko Kirino, Kenichiro Hata, Osamu Ohara, Tomohiro Morio, Toshiro Hara

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)185-190
Number of pages6
JournalNeonatology
Volume107
Issue number3
DOIs
Publication statusPublished - Apr 6 2015

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Biology

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