Clinical Presentation and Molecular Identification of Four Uncommon Alpha Globin Variants in Thailand

Abstract

Alpha thalassemia is the most common genetic disease in the world with the prevalence of carriers ranging from 5-50% in several populations. Coinheritance of two defective α-globin genes usually gives rise to a symptomatic condition, hemoglobin (Hb) H disease. Previously, it has been suggested from several studies in different populations that nondeletional Hb H disease (--/α^Tα or --/αα^T) is generally more severe than the deletional type (--/-α). In this report, we describe four rare nondeletional α-thalassemia mutations in Thai individuals, including initiation codon mutation (HBA2:c.1delA), donor splice site mutation (IVSI-1, HBA1:c.95 + 1G>A), Hb Queens Park (HBA1:c.98T>A) [α32(B13)Met>Lys], and Hb Westmead (HBA2:c.369C>G) [α122(H5)His>Gln]. Interactions of the first three mutations with the α⁰-thalassemia resulted in nondeletional Hb H disease; however, their clinical presentations were rather mild and some were detected accidentally. This suggests that a genotype-phenotype correlation of α-thalassemia syndrome might be more heterogeneous and so the type of mutation does not simply imply the prediction of the resulting phenotype. Our data will be of use in future genetic counseling of such conditions that are increasingly identified thanks to the improvement of molecular analysis in routine laboratories.

The prevalence of thalassemia in mainland China: evidence from epidemiological surveys

“…In addition, non-deletional α-thalassemia is not rare. α WS α, which is rather rare in other parts of the world 32 , is the most prevalent non-deletion type of α-thalassemia, with a gene frequency of 0.26%. Several studies on different populations have suggested that the non-deletion types of Hb H disease(--/α T α) are usually more severe than the deletion types (--/-α), with greater anaemia, jaundice, splenomegaly and early anaemic symptoms, and a higher proportion of patients who require blood transfusion and splenectomy 28, 33 .…”

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation

“…The clinical signs of DENV infection reflect the different levels of severity including dengue fever or dengue hemorrhagic fever, or dengue shock syndrome (DSS). Patients with more severe forms of the disease display hemorrhagic disorders, including plasma leakage, thrombocytopenia, hemoconcentration, and multi-organ failure [ 1 – 6 ]. Liver transaminase (alanine transaminase [ALT] and aspartate transaminase [AST]) levels increase in both DENV-infected patients [ 7 – 10 ] and murine models of DENV infection [ 11 – 15 ].…”

Clinical and molecular genetic features of Hb H and AE Bart’s diseases in central Thai children

“…Recently, it has been reported in Thai population. 16 Our patient may be one of those cases who carries this rare mutation. In our study, comparison of clinical spectrum and severity between patients with Hb H disease and AE Bart’s disease was evaluated.…”