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Introduction: Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A).Materials and Methods: HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia.Results and Discussion: Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA.Conclusion: The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother. [ABSTRACT FROM AUTHOR]

p53gene mutation is not a frequent event in the tumorigenesis of lymphomas and the expression of p53 protein is independent ofp53gene mutations. The present study aimed to investigate mutations in thep53gene in a series of extranodal B-cell lymphomas, and its association with p53 protein expression. A total of 52 cases were graded histologically into Grade 1, Grade 2 and Grade 3 tumors and p53 protein expression was detected using immunohistochemistry. Mutations in thep53gene were analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and mobility shifts were confirmed by direct sequencing. The tumors comprised 26 (50%) Grade 1, 9 (17%) Grade 2 and 15 (29%) Grade 3. A high proportion of Grade 2 (25%) tumors expressed p53 protein (P = 0.051) and carriedp53gene mutation (33%) (P = 0.218). However, p53 protein expression was not associated withp53gene mutations (P = 0.057). Transversion mutations (88%) were more frequently detected than transition mutations (12%). The present study revealed thatp53gene mutations and p53 protein expression occurred in higher frequencies in Grade 2 tumors, which may be of pathogenetic importance. The high frequency of transversion mutations may reflect the influence of an etiological agent in the tumorigenesis of mucosa-associated lymphoid tissue (MALT lymphoma). [ABSTRACT FROM AUTHOR]

Molecular characterization of the compound heterozygous condition--[supG]γ([supA]γδΒ)[supo]/Β-thalassemia--in four families showing mild Β-thalassemia intermedia was carried out using DNA amplification techniques. Using the Amplification Refractory Mutation System (ARMS) to confirm the Β-mutations and DNA amplification to detect the 100-kb Chinese-specific [supG]γ([supA]γδΒ)[supo]-deletion, two families were confirmed to possess [supG]γ([supA]γδΒ)[supo]/&Beta-thalassemia with the IVSII No. 654 Β[sup+]-allele. In the third family, the [supG]γ([supA]γδΒ)[supo]-deletion was confirmed in the father and the mother was a Β-thalassemia carrier with the cd 41-42 Β[supo]-allele. Their affected child with [supG]γ([supA]γδΒ)[supo]/Β-thalassemia was found to be transfusion dependent. The same [supG]γ([supA]γδΒ)[supo]-deletion and Β-thalassemia (cd 41-42) was also confirmed in a fourth family. In addition, the mother was also diagnosed with Hb H disease (genotype-α[sup3.7]/[sup-SEA]). Both the children were found to possess [supG]γ([supA]γδΒ)[supo]/Β-thalassemia but they were not transfusion dependent and this could be due to co-inheritance of α-thalassemia-2 (genotype-α[sup3.7]/αα) in the children together with their compound heterozygous condition. [ABSTRACT FROM AUTHOR]

β-Thalassemia is a public health problem where 4.5% of Malaysians are β-thalassemia carriers. The genetic disorder is caused by defects in the β-globin gene complex which lead to reduced or complete absence of β-globin chain synthesis. Five TaqMan genotyping assays were designed and developed to detect the common β-thalassemia mutations in Malaysian Malays. The assays were evaluated with 219 "blinded" DNA samples and the results showed 100% sensitivity and specificity. The in-house designed TaqMan genotyping assays were found to be cost- and time-effective for characterization of β-thalassemia mutations in the Malaysian population. [ABSTRACT FROM AUTHOR]