Identification of a Novel Gene Mutation in a Chinese Pedigree with X-linked Thrombocytopenia.

BACKGROUND: X-linked thrombocytopenia (XLT) is a milder form of Wiskott-Aldrich syndrome (WAS), characterized predominantly by thrombocytopenia with small-sized platelets. Mutations in the WAS gene are responsible for the disease. We herein detected a new mutation in the WAS gene responsible for XLT in a 3-generation Chinese pedigree.

METHODS: Peripheral blood samples were collected from 7 members in the family. WAS gene was amplified from genomic DNA isolated from leucocytes, and then direct sequencing was performed.

RESULTS: Three male members of this family (the proband, his younger brother and maternal uncle) had thrombocytopenia and decreased mean platelet volume. A homozygous mutation (T>C) was found at nucleotide position 319 in exon 3, causing the amino acid Tyr (T) to be abnormally changed to His (H) at position 107. Two female members (the proband's mother and grandmother) were carriers of the mutation.

CONCLUSIONS: XLT is easy to misdiagnose as immune thrombocytopenic purpura (ITP). The diagnosis of XLT should be considered in any male with congenital microthrombocytopenia or early onset of microthrombocytope-nia (< 7 fL). This article adds to the growing number of known mutations associated with XLT.