Interaction of Hb South Florida (codon 1; GTG1ATG) and HbE, with b-thalassemia (IVS1-1; G1A): expression of different clinical phenotypes

• Published in: European journal of pediatrics Vol. 168; no. 9; pp. 1049 - 1054
• Main Authors: Tan, Jin-Ai Mary Anne, Tan, Kim-Lian, Omar, Khairul Zaman, Chan, Lee-Lee, Wee, Yong-Chui, George, Elizabeth
• Format: Journal Article
• Language: English
• Published: 01.09.2009
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-008-0877-9

Introduction: Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-b-thalassemia generally manifests with severe anemia where individuals exhibit b-thalassemia major with regular blood transfusions or b-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three b-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G1A). Materials and methods: HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare b-hemoglobin variant, and its interactions with other b-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to b super(o)-thalassemia. Results and discussion: Fifteen mutations along the b-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 b-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a b-thalassemia carrier phenotype in the mother.