Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 77

Tabl e 3. 6. α -Variants and deletional forms of α -thalassemia (Source: [ 143 ]).

Variant Amino acid subtitution in α -globin

Hb Evanston Trp14 → Arg

Hb Hasharon Asp47 → His

HbG Philadelphia Asn68 → Lys

HbQ Mahidol Asp74 → His

Hb Duan Asp75 → Ala

Hb Nigeria Ser81 → Lys

HbJ Capetown Arg92 → Gln

HbJ Tongariki Ala115 → Asp

-globin
chains. An elevated proportion of hemoglobin-F and other variants, such as
hemoglobin-S (

In humans, hemoglobin variants include variants of α -, β -, γ -, and δ

2 ), correspond to hemoglobinopathies.
Thalassemia is caused by hemoglobin variants (deletional and non-deletional
forms of gene mutations). Thalassemia has most often an autosomal recessive
pattern of inheritance, both parents being unaffected carriers of a hemoglobinopathy
trait.
α

2 )and-C(

α 2 β α 2 β

-Thalassemia results from deletions of one or both HBA1 and HBA2 genes.

The determinant is associated with many different Hb variants (Table 3.6 ). Non-

deletion mutations that are mainly associated with the HBA2 gene, affecting mRNA
translation and processing, or causing post-translational instability, also generate
α

− α

-thalassemia.
Hemoglobin Bart's hydrops fetalis syndrom is one of the major hemoglobi-
nopathies responsible for α thalassemia. α Thalassemia can indeed cause hydrops

fetalis when all 4 of the genetic loci for -globin are deleted or affected by

mutation. Hydrops fetalis is characterized by edema in at least 2 fetal compartments
(hydrops allantois and hydrops amnion correspond to fluid accumulation in the
allantoic and amniotic space respectively). Thalassemia can coexist with other
hemoglobinopathies.
The most severe case of

α

α -thalassemia is characterized by a defective or or

lacking production of α -globin chains from the HBA1 and HBA2 genes, which

encode hemoglobin α 1and α 2chains. Hemoglobin Barts (Bartholomew) consists

of 4 chains. It has a very high affinity for oxygen, thus hampering oxygen delivery

to cells.
Hemoglobin-H (HbH) is a

γ

chains form unstable
tetramers, which have abnormal oxygen dissociation curves. It has a higher affinity
for oxygen than normal hemoglobin, thereby delivering a low quantity of oxygen to
cells.
Inherited

β -chain tetramer. The excess β

-thalassemia is characterized not only by a reduced or absent synthesis
of hemoglobin

β

β chain, but also an elevated HbF concentration. In thalassemia

minor , a single -globin allele (among 2 alleles) bears a mutation that causes

microcytic anemia; in thalassemia major , both alleles undergo mutations.

β