A base substitution (T→C) in codon 29 of the α2‐globin gene causes α thalassaemia

Abstract

Summary. We have identified three individuals of Greek or Greek Cypriot origin with an atypical form of HbH disease characterized by a severe hypochromic microcytic anaemia associated with relatively small amounts of HbH in the peripheral blood. Molecular analysis has shown that each is a compound heterozygote for a previously described mutation affecting the poly A addition signal (AATAAA→ÁTAAG) and a previously undescribed mutation involving a T→C transition in codon 29 of the α2 gene causing a leucine→pro‐line substitution. Although this mutation would be expected to produce an unstable haemoglobin and hence a haemolytic anaemia, simple heterozygotes for the α29Leu→Pro mutation have the phenotype of α‐thalassaemia trait.

Hb Agrinio [α29(B10)Leu→Pro (α2)] in Combination with – –MED IResults in a Severe Form of Hb H Disease

“…None of the four --MED I /α Poly 2 α and none of the 21 --MED I /α −5 nt α patients identified by the Cyprus Thalassaemia Centre (Archbishop Makarios III Hospital, Nicosia, Cyprus) are transfusion-dependent (14,15). Evidence for the severity of the Hb Agrinio mutation is corroborated by another report (5) where one out of three patients with the α T-Saudi α/α Agrinio α genotype required regular blood transfusions. Furthermore, one of two homozygous Hb Agrinio patients identified by the Cyprus Thalassaemia Centre is also transfusion-dependent.…”

“…Since subject II-3 was married to an αα/--MED I carrier (II-5), there was a risk that the fetus would carry the unknown determinant along with the --MED I mutation from the father, resulting in a severe phenotype. Direct sequencing (subject II-3) showed a C→T change at codon 29 (CTG→CCG) of the α2-globin gene which causes an amino acid substitution of leucine to proline, resulting in the Hb Agrinio chain variant (5). Subject I-1 was then tested by restriction enzyme digestion with MspI and found to be heterozygous for Hb Agrinio.…”

“…Hb Agrinio (α Agrinio α), a nondeletional α-globin mutation, was first identified in members of three families of Greek or Greek Cypriot origin (5). This is a T→C substitution at codon 29 (CTG→CCG) leading to the conversion of leucine to proline.…”

“…Compound heterozygotes, α TSaudi α/α Agrinio α, present with an atypical form of Hb H disease, with hypochromic microcytic anemia, hepatosplenomegaly but relatively low levels of Hb H and few Hb H inclusion bodies. Simple heterozygotes for Hb Agrinio have the phenotype of an α-thal trait and do not exhibit the hemolytic anemia usually associated with unstable hemoglobins (Hbs) (5) and in that, resembles another unstable α-globin variant, Hb Quong Sze [α125(H8)Leu→Pro (α2)], also a CTG→CCG substitution (6).…”

A study of Serological and Hematological Parameters in Thalassaemic Patients of Gujarat, Western India

“…On the basis of the affected globin chain, the thalassemias are classified into α or β types. The β thalassemia is prevalent throughout the world while α is found more in the Mediterranean region, [1] Middle East, [2], [3], [4] South Asia [5], [6] and South East Asia. [7], [8], [9] The hematological parameters in the thalassemic patients vary with the type and severity of anemia.…”