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Wiskott- Aldrich syndrome ( WAS) is an X-linked recessive primary immunodeficiency disorder caused by mutations in the gene encoding the WAS protein ( WASP). Classic WAS is characterized by thrombocytopenia with small-sized platelets, recurrent infections, eczema and increased susceptibility to autoimmune diseases and haematologic malignancies. Here, we reported on seven unrelated Thai individuals with classic WAS. In addition to clinical and immunologic characterization, mutation analysis by PCR-sequencing the entire coding region of WASP was performed. Recurrent and novel mutations were successfully identified. A nonsense mutation, the c.55 C> T (p. Q19 X), has not been previously described, expanding the mutational spectrum of WASP. The patient with this newly described mutation developed cow's milk allergy manifesting as angioedema and urticaria and had cytomegalovirus infection that was successfully treated with long-term ganciclovir. This study reported long-term follow-up of seven patients with molecular confirmation of WAS and infrequent features in the patient with classic WAS carrying the novel nonsense mutation. [ABSTRACT FROM AUTHOR]

Tammachote R, Janklat S, Tongkobpetch S, Suphapeetiporn K and Shotelersuk V. Holocarboxylase synthetase deficiency: novel clinical and molecular findings. Multiple carboxylase deficiency (MCD) is an autosomal recessive metabolic disorder caused by defective activity of biotinidase or holocarboxylase synthetase (HLCS) in the biotin cycle. Clinical symptoms include skin lesions and severe metabolic acidosis. Here, we reported four unrelated Thai patients with MCD, diagnosed by urine organic acid analysis. Unlike Caucasians, which biotinidase deficiency has been found to be more common, all of our four Thai patients were affected by HLCS deficiency. Instead of the generally recommended high dose of biotin, our patients were given biotin at 1.2 mg/day. This low-dose biotin significantly improved their clinical symptoms and stabilized the metabolic state on long-term follow-up. Mutation analysis by polymerase chain reaction-sequencing of the entire coding region of the HLCS gene revealed the c.1522C>T (p.R508W) mutation in six of the eight mutant alleles. This suggests it as the most common mutation in the Thai population, which paves the way for a rapid and unsophisticated diagnostic method for the ethnic Thai. Haplotype analysis revealed that the c.1522C>T was on three different haplotypes suggesting that it was recurrent, not caused by a founder effect. In addition, a novel mutation, c.1513G>C (p.G505R), was identified, expanding the mutational spectrum of this gene. [ABSTRACT FROM AUTHOR]

Abstract: Non-syndromic cleft lip with or without cleft palate (CL/P) has a complex etiology with several genetic and environmental factors playing a role. The poliovirus receptor related-1 gene (PVRL1) has been shown to underlie a syndromic form of CL/P and, in some populations, contribute to non-syndromic CL/P. To investigate whether mutations in PVRL1 play a part in the formation of non-syndromic CL/P in the Thai population, 100CL/P patients were analyzed for mutations in PVRL1 by polymerase chain reaction amplification and direct sequencing of all the coding regions of its alpha isoform. Of this series of patients, one was found to be heterozygous for 1183G>A in exon 6, expected to result in the substitution of a valine by a methionine at position 395 (V395M). This mutation was not found in 200 unaffected Thai control individuals. The valine position is conserved across all known mammalian PVRL1 sequences. In conclusion, a novel non-synonymous PVRL1 mutation was found in a Thai patient with non-syndromic CL/P, suggesting a possible etiologic role of PVRL1 in non-syndromic CL/P across different populations. [Copyright &y& Elsevier]