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Beta Thalassemia
There are hundreds of mutations within the beta globin gene, but approximately
20 different alleles comprise 80% of the mutations found world wide. Within
each geographic population there are unique mutations. Individuals who
have beta thalassemia major are usually homozygous for one of the common
mutations, or heterozygous for one of the common mutations and one of
the geographically-unique mutations. Both lead to absence of beta globin
chain production.
The beta thalassemia syndromes are much more diverse than the alpha thalassemia
syndromes due to the diversity of the mutations that produce the defects
in the beta globin gene. Unlike the deletions that constitute most of
the alpha thalassemia syndromes, beta thalassemias are caused by mutations
on chromosome 11 that affect
all aspects of beta globin production: transcription,
translation,
and the stability of the beta globin product. Most hematologists feel
there are three general categories of beta thalassemia: beta thalassemia
trait, beta thalassemia intermedia and beta thalassemia major.
Splice site mutations also occur and are of clinical consequence, when
combined with a thalassemia mutation. Three splice site mutations occur
in exon 1 of the beta globin gene. These mutations result in three different
abnormal hemoglobins: Malay, E, and Knossos. Hemoglobin E is a
very common abnormal hemoglobin in the Southeast Asian population, and
when paired with a b0 thalassemia
mutation, can produce severe transfusion-dependent (Eb0)
thalassemia. Hemoglobin E is described in the next section on variant
hemoglobins. <next>
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