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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]

Co-inheritance of α-thalassemia with homozygosity or compound heterozygosity for Β-thalassemia may ameliorate Β-thalassemia major. A wide range of clinical phenotypes is produced depending on the number of α-thalassemia alleles (-α/αα--/αα, --/-α). The co-inheritance of Β-thalassemia with α-thalassemia with a single gene deletion (-α/αα) is usually associated with thalassemia major. In contrast, the co-inheritance of Β-thalassemia with two α-genes deleted in cis or trans (--/αα or -α/-α) generally produces Β-thalassemia intermedia. In Southeast Asia, the most common defect responsible for α-thalassemia is the Southeast Asian (SEA) deletion of 20.5 kilobases. The presence of the SEA deletion with Hb Constant Spring (HbCS) produces HbH-CS disease. Co-inheritance of HbH-CS with com-pound heterozygosity for Β-thalassemia is very rare. This study presents a Malay patient with HbH-CS disorder and Β°/Β+-thalassemia. The SEA deletion was confirmed in the patient using a duplex-PCR. A Combine-Amplification Refractory Mutation System (C-ARMS) technique to simultaneously detect HbCS and Hb Quong Sze confirmed HbCS in the patient. Compound heterozygosity for CD41/42 and Poly A was confirmed using the ARMS. This is a unique case as the SEA α-gene deletion in cis (--SEA/αα) is generally not present in the Malays, who more commonly posses the two a-gene deletion in trans (-α/-α). In addition, the Β-globin gene mutation at CD41/42 is a common mutation in the Chinese and not in the Malays. The presence of both the SEA deletion and CD41/42 in the mother of the patient suggests the possible introduction of these two defects into the fam-ily by marriage with a Chinese. [ABSTRACT FROM AUTHOR]