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

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Wiskott-Aldrich Syndrome Protein
Wiskott-Aldrich Syndrome
Uniparental Disomy
X Chromosome Inactivation
Mothers
Mutation
Thrombocytopenia
Minisatellite Repeats
Chromosomes, Human, Pair 6
Nonsense Codon
Eczema
X Chromosome
Microarray Analysis
DNA Sequence Analysis
Genes
Single Nucleotide Polymorphism
Exons
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Biology

Cite this

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

In: Neonatology, Vol. 107, No. 3, 06.04.2015, p. 185-190.

Research output: Contribution to journalArticle

Takimoto, Tomohito ; Takada, Hidetoshi ; Ishimura, Masataka ; Kirino, Makiko ; Hata, Kenichiro ; Ohara, Osamu ; Morio, Tomohiro ; Hara, Toshiro. / 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. In: Neonatology. 2015 ; Vol. 107, No. 3. pp. 185-190.
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