Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes.
BACKGROUND
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).


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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Tan
Jin-Ai Mary Anne
JA
Department of Molecular Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur, Malaysia. jamatan@hotmail.com
Tan
Kim-Lian
KL
Omar
Khairul Zaman
KZ
Chan
Lee-Lee
LL
Wee
Yong-Chui
YC
George
Elizabeth
E
D000483:Alleles; D001803:Blood Transfusion; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006529:Hepatomegaly / Q000150:complications; D006801:Humans; D007223:Infant; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D022821:RNA Splice Sites; D013163:Splenomegaly / Q000150:complications; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics* / Q000628:therapy
D003062:Codon; D017931:DNA Primers; D006455:Hemoglobins, Abnormal; D022821:RNA Splice Sites; C050301:hemoglobin South Florida