Borderline hemoglobin A2 levels in northern Thai population: HBB genotypes and effects of coinherited alpha-thalassemia

First report of the spectrum of δ‐globin gene mutations among women of reproductive age in Fujian area—Discrimination of δ‐thalassemia, α‐thalassemia, and Iron Deficiency Anemia

“…Mutations that occur on the beta globin gene generally tend to an increased HbA 2 levels, but in some situations, β thalassemia traits are not associated with raised HbA 2 . Furthermore, β thalassemia in combination with δ‐thalassemia is described, as well as co‐association with α‐thalassemia, which are sources of diagnostic pitfalls in carrier screening and counseling 9‐13 …”

“…However, in some situations, normal, borderline, or reduced HbA 2 level may still be associated with β thalassemia trait, which will make difficulty in the setting of genetic counseling, whereas a decreased HbA 2 level may lead to the suspicion of IDA, δ‐thalassemia, and α‐thalassemia. What's more, IDA needs to be confirmed by other biological parameters or by a therapeutic correction trial and δ‐thalassemia, α‐thalassemia needs DNA sequencing or other specific analysis 8‐13 …”

“…Mutations that occur on the beta globin gene generally F I G U R E 1 Sequence results of the 2 known and 3 novel δ-globin gene mutations, A, −77 T > C mutation; B, −30 T > C mutation; C,-44G > A mutation; D,CD87C > T mutation; E,CD134T > A mutation tend to an increased HbA 2 levels, but in some situations, β thalassemia traits are not associated with raised HbA 2 . Furthermore, β thalassemia in combination with δ-thalassemia is described, as well as co-association with α-thalassemia, which are sources of diagnostic pitfalls in carrier screening and counseling [9][10][11][12][13]. To date, 137 δ globin gene mutations have been reported, as summarized in http://globin.cse.psu.edu/hbvar/ menu.html (accessed March 12, 2020).…”

Compound heterozygosity of a silent beta‐thalassemia mutation at the 3′‐untranslated region (HBB: c.*132 C>T) and beta‐zero thalassemia results in thalassemia intermedia

“…Previously reported HBB mutations that are associated with borderline Hb A 2 levels in our population in Northern Thailand were the CAP site (c.‐50 A>C) and Hb Dhonburi (c.380 T>G) mutations . Mutations in the 3′‐UTR were not detected in the previous study of 106 blood samples with borderline Hb A 2 levels between 3.1 and 3.9% so these mutations are likely quite rare.…”

Prenatal Genetic Counseling in a Chinese Pregnant Woman With Rare Thalassemia: A Case Report

“…Betathalassemia usually has a high HbA2 level (Mosca et al, 2009) only when β-globin silent mutations, for example, very slight microcytosis, are associated with consistent residual output of Hb beta chains and with normal or borderline HbA2 and normal RBC indexes (Galanello and Origa, 2010). Beta-thalassemia coinheritance of iron deficiency or δ-thal may reduce the increased HbA2 levels typical of β-thalassemia carriers to normal (Giambona et al, 2006;Galanello and Origa, 2010;Chaweephisal et al, 2019). Hemoglobinopathies complicated with other types of thalassemia may present clinical manifestations of thalassemia to various degrees (Xu et al, 2004;Singer, 2009;Xiong et al, 2010;Lin et al, 2012;Zhao et al, 2013).…”