The milder form, X-linked thrombocytopenia (XLT; MIM 313900), is usually limited to thrombocytopenia with absent or minor infections and eczema [1-4]. Patients with severe WAS mostly die from infection or bleeding within the first decades of life. Hematopoietic CH5424802 stem cell transplantation (HSCT) remains the only curative therapy for WAS [5,
6]. The WASP gene contains 12 exons with coding regions of 1823 bp. Its gene product, WASP, contains 502 amino acids and has five major functional domains involved in intracellular signalling and actin cytoskeleton reorganization in response to cell stimulation. The WASP is predominantly expressed in hematopoietic cell lineages. Absent or defective WASP leads to dysfunctions in different leucocyte subgroups involved in innate, humoral and cellular immunity as well as impaired platelet formation [2, 7]. At least 300 different disease-causing mutations in WASP have been identified with the most common being missense mutations (Human Gene
Mutation Database, http://www.hgmd.cf.ac.uk, accessed July, 2012) [8-10]. Six mutational hotspots are also described. Loss-of-function mutations in the WASP gene are responsible for WAS and XLT, whereas gain-of-function mutations in the region encoding the conserved GTPase binding domain of find more WASP lead to X-linked congenital neutropenia [8, 11, 12]. Here, we described seven unrelated Thai patients with classic WAS including rare manifestations and identified a novel nonsense mutation. Seven unrelated patients from different families including one previously reported were included in this study [13]. Diagnosis of classic WAS was based on clinical manifestations of thrombocytopenia, recurrent infections and eczema. The patients’ age of onset ranged from 6 days to 8 months. The patients aged from 4 months to 5 years at the time of diagnosis. Using previously published scoring criteria [14], patients were assigned scores to describe Urease their clinical severity. All patients had scores of 4 or higher. Clinical details and laboratory findings are shown
in Table 1. Of these seven patients, two received HSCT. The study was approved by the institutional review board of the Faculty of Medicine of Chulalongkorn University, and written informed consent was obtained from each family in accordance with the Declaration of Helsinki. Peripheral blood samples were collected from the probands and their available parents. Total RNA and genomic DNA were extracted from peripheral blood leucocytes using Qiagen RNA and DNA extraction kits (Qiagen, Valencia, CA, USA). Reverse transcription was performed using ImProm-II™ reverse transcriptase (Promega, Madison, WI, USA), according to the manufacturer’s recommendations. WASP entire coding regions were PCR-amplified and sequenced as previously described [13].
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