CLINICAL CASES
113
D efinitions
Erythropoiesis: Erythropoiesis is the development of mature red blood
cells containing hemoglobin (erythrocytes) from pluripotential stem
cells via a linear cascade.
Frameshift mutation: Insertion or deletion of a number of nucleotides that
are not divisible by three into a coding sequence, thereby causing an
alteration in the reading frame of the entire sequence downstream of the
mutation.
Locus control region: Regulatory region which is believed to regulate
transcription by opening and remodeling chromatin structure. It may
also have enhancer activity.
Promoter sequence: A regulatory region present at a short distance
upstream from the 5' end of a transcription start site that acts as the bind-
ing site for RNA polymerase to initiate transcription.
Thalassemia: A group of genetic disorders that is characterized by the
absence of or reduced synthesis of one or more of the four globin chains
in hemoglobin. The sequelae can range from benign to fatal, depending
on the severity of the decrease in the globin chain.
Transposons: These are segments of DNA that can move around to different
positions in the genome of a single cell. In the process, they may cause
mutations and increase (or decrease) the amount of DNA in the genome.
These mobile segments of DNA are sometimes called “jumping genes.”
D ISC U SSIO N
Thalassemia is a common condition in the Mediterranean region and its clini-
cal features were described as early as 1925. The term
thalassemia
is coined
from the Greek word, which means “the sea.” Mendelian transmission of tha-
lassemia was discovered in 1938. Later, it became apparent that thalassemia is
not a single disease but a group of genetic disorders, all of which arise from
abnormalities in hemoglobin synthesis. The thalassemias are characterized
by the absence or reduced synthesis of one or more of the four globin
chains of hemoglobin. There are four different genetic loci that control the
formation of a-, P-, y-, and 8-chains of hemoglobin (Hb). Fetal Hb (HbF)
is formed from two a- and two y-chains. In adults, the y-chain is replaced
by the P- and 8-chains, which combine with two a-chains to form HbA
(a2P2, approximately 97 percent) and HbA2 (a2y2, approximately 3 percent)
(Figure 12-1). In the late 1970s, the gene was found to be localized to chro-
mosome 16, whereas the P-, y-, and 8-genes were clustered on chromosome
11. Thus, although thalassemia does not occur in the fetus since the P-globin
genes are activated only after birth, prenatal diagnosis is possible.
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