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Chapter 7 Genetic disorders of haemoglobin / 107

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Figure 7.23 α - Thalassaemia: antenatal diagnosis by gap - PCR analysis. The common α - thalassaemia deletion
mutations are diagnosed using primers which bind to fl anking sequences on either side of the deletion break-
point. For the – MED deletion, the primer pair (1 & 2) produce an amplifi ed product of 650 base pairs (bp) in
size. The primers are too far apart to amplify the normal DNA sequence, so a third primer (3) is included that is
complementary to the deleted sequence near one of the breakpoints. This produces a normal fragment of
1000 bp. The gel electrophoresis photograph shows the mother ’ s DNA (lane 1, heterozygous), father ’ s DNA
(lane 2, heterozygous), CVS DNA (lane 3, normal) and two homozygous control DNAs (lanes 4 & 5). (Courtesy
of Dr. J. Old.)
■ Genetic disorders of haemoglobin fall into disorders showing mild to moderate

two main groups: anaemia and is usually caused by variants

1 The thalassaemias in which synthesis of of β - thalassaemia.

the α or β globin chain is reduced. ■ The most frequent structural defect of

2 Structural disorders in which an haemoglobin is the sickle mutation in the SUMMARY
abnormal haemoglobin is produced. β - globin chain causing, in the homozygous

■ The α - or β - thalassaemias occur clinically form, a severe haemolytic anaemia,

as minor forms with microcytic associated with vaso - occlusive crises.
hypochromic red cells and a raised red cell These may be painful affecting bone or
count with or without anaemia. Total affect soft tissues (e.g. chest, spleen or
absence of function of all four α globin central nervous system). Crises may also
genes causes hydrops fetalis. be haemolytic or aplastic.

■ Total absence of function of both β globin ■ Antenatal diagnosis using PCR technology

genes causes β - thalassaemia major, a to amplify chorionic villous DNA is used to

transfusion - dependent anaemia associated detect severe genetic defects of
with iron overload. Thalassaemia haemoglobin production, with termination
intermedia is a clinical term for a group of of the pregnancy if appropriate.

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