Unique and Recurrent WAS Gene Mutations in Wiskott-Aldrich Syndrome and X-Linked Thrombocytopenia

Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are allelic phenotypes caused by defects of the WAS gene. Fourteen distinct mutations including seven novel gene defects in 16 WAS and four XLT patients were identified by single strand conformation polymorphism analysis and DNA sequ...

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Bibliographic Details
Published in:Blood cells, molecules, & diseases molecules, & diseases, 1999-08, Vol.25 (4), p.218-226
Main Authors: Thompson, Lisa J, Lalloz, Michel R.A, Layton, D.Mark
Format: Article
Language:English
Subjects:
African Continental Ancestry Group - genetics
Asian Continental Ancestry Group - genetics
European Continental Ancestry Group - genetics
Family Health
Female
Genetic Carrier Screening
Haplotypes
Humans
Male
Mutation - genetics
Pedigree
Polymorphism, Single-Stranded Conformational
Pregnancy
Prenatal Diagnosis
Sequence Analysis, DNA
Thrombocytopenia - genetics
United Kingdom - epidemiology
Wiskott-Aldrich Syndrome - genetics
Wiskott-Aldrich syndrome, X-linked thrombocytopenia, X-linked disease, mutation, prenatal diagnosis, CpG, polymorphism
X Chromosome
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Summary:Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are allelic phenotypes caused by defects of the WAS gene. Fourteen distinct mutations including seven novel gene defects in 16 WAS and four XLT patients were identified by single strand conformation polymorphism analysis and DNA sequencing of the WAS gene. Eleven (79%) of these mutations are located within exons 1 to 4 with clustering in exon 2. Carrier detection in 33 at-risk females and prenatal diagnosis at 12 weeks gestation in one family with a novel WAS mutation was performed by direct mutation analysis. A remarkably high frequency (72%) of point mutations involved CpG dinucleotides. C→T or G→A transitions at CpG sites were identified in all isolated WAS cases (n=7). Allele frequencies for the dinucleotide repeat at locus DXS6940 were determined in Northern European, African and Asian populations. Mutation screening alone or in combination with analysis of polymorphic loci DXS6940 and DXS255 delineated the germline origin of a unique insertion mutation and four recurrent CpG mutations, three of which arose spontaneously during maternal gametogenesis.
ISSN:1079-9796
1096-0961
DOI:10.1006/bcmd.1999.0247