Normal Hb A₂β-Thalassemia Trait: Frameshift Mutation (HBB: c.187_251dup) inCiswith the Hb A_2’δ-Globin Gene Missense Mutation (HBD: c.49G>C)

Abstract

We report the case of a father and daughter who are heterozygous for a duplication of 65 bp within exon 2 of the β-globin gene, resulting in an altered and truncated β-globin chain that is predicted to be non functional. The β-globin gene mutation is in cis with the common Hb A2 ' missense mutation of the δ-globin gene (HBD: c.49G>C), resulting in β-thalassemia (β-thal) trait with normal levels of Hb A2. This is the second report of this β(0)-thal mutation, and both families were associated with the Hb A2 ' variant and normal levels of Hb A2. Laboratories should be aware of the rare occurrence of β-thal trait with normal levels of Hb A2.

Phenotypic Expression of Known and Novel Hemoglobin A2-Variants, Hemoglobin A2-Mae Phrik [Delta 52(D3) Asp > Gly, HBD:c.158A > G], Associated with Hemoglobin E [Beta 26(B8) Glu > Lys, HBB:c.79G > A] in Thailand

“…Patients who are heterozygous or even homozygous for this variant usually have no clinically significant problems, since Hb A 2 constitutes only a small proportion of the total Hb content. However, the interaction of δ-Hb variants with other variants or other thalassemias can lead to an erroneous interpretation of routine laboratory diagnostic test results [ 4 , 6 , 12 , 25 ]. This study reported known and novel Hb A 2 -variants coinherited with Hb E in Southeast Asia.…”

“…Although most are non-pathological variants, coinheritance with β- or α-thalassemia or other variants results in diverse clinical syndromes. This may lead to diagnostic problems, as the amount of Hb A 2 observed is often reduced to a value within the range usually observed in normal individuals [ 4 , 5 , 6 ]. These δ-Hb variants are especially prevalent in the Mediterranean region and are occasionally seen in other regions such as Southeast Asia [ 7 , 8 , 9 ].…”

Heterozygous β‐thalassemia with complete absence of hemoglobin A2 in a Chinese adult

“…Through genetic counseling and the option of prenatal testing, such a couple can opt to bring to term only those pregnancies in which the fetus is unaffected. Elevation of HbA 2 is the most important feature in the detection of heterozygous b-thalassemia, but there are sometimes bthalassemia heterozygotes with normal HbA 2 , compromising the screening effectiveness [1][2][3][4][5]. b-thalassemia with the absence of HbA 2 is very rare.…”