Homozygosity for the Severe β⁺-Thalassemia Mutation [IVS-I-5 (G>C)] Causes the Phenotype of Thalassemia Trait: An Extremely Rare Presentation

Abstract

The thalassemias are the most common single gene disorder known to mankind. The phenotype of thalassemia depends upon the underlying gene defect in addition to many modulating factors. As the literature describes, inheritance of a β(0) genotype in the homozygous state results in the development of β-thalassemia (β-thal) major with key clinical features being transfusion dependency, physical abnormalities and iron overload. IVS-1-5 (G>C) is the severe β(+) allele whose homozygosity results in severe β-thal. We describe a patient who was asymptomatic until screened and was found to have mild anemia. Detailed analysis revealed the presence of the IVS-I-5 mutation in a homozygous state that was unlikely to present as a transfusion independent state. The study of such cases emphasizes the complexity of genetic interactions that underlie the phenotype of β-thal and highlight the importance of the regulation of Hb F production in β-thal syndromes. Simultaneous inheritance of some loci that modulate Hb F levels probably causes high levels of total hemoglobin (Hb) and to be transfusion independent.

Molecular Characterisation of α‐ and β‐Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia

“…IVS 1–5 (G>C) was found only in the Jah Hut subethnic group with an allelic frequency of 1.9%. Both IVS 1–5 (G>C) and Cd 26 (G>A) are the two most common β ‐thalassaemia alleles in the Malays in Malaysia and have been reported in the Javanese (Teh et al., ), Thai (Boonyawat et al., ; Thedsawad et al., ), Myanmar (Ne‐Win et al., ), Indian (Bohara et al., ; Colah et al., ) and Azerbaijan (Akbarova, ) populations.…”

Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity

“…Thirtyseven (72.55%) SBT patients had IVS 1-5 (G → C) mutation, 11(21.57%) had IVS 1-1 (G → A) mutation, 2 had CD-16 mutation and one SBT patient had CD 41/42 mutation. Even though IVS 1-5 (G → C) clinically behaves as an β 0 mutation for all practical purposes SBT patients with IVS 1-5 (G → C) was classified separately as severe Hb S/β+ as it is known to produce some Hb A (n = 37) [20][21][22][23]. SBT patients identified with other β mutations were all unquestionably severe mutations and were classified as Hb S/β 0 type (n = 14).…”

A Review of Molecular Events of Cadmium-Induced Carcinogenesis

“…In addition, prolonged oxidative stress causes changes in cellular redox homestasis and leads to abnormal activation of redox-sensitive signaling molecules (38). Further oxidative stress, such as observed in Cd-exposure, can cause genetic and epigenetic changes, uncontrolled cell growth, and abnormal cellular signaling, all of which are primary mechanisms involved in metal-mediated carcinogenesis (39) (40) (41). …”