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Variant Hemoglobins
Any hemoglobin that contains a mutation is a variant hemoglobin. A mutation
can involve a delete of all or a portion of the gene leading to a reduced
or absent production of globin proteins, or small changes in the DNA that
affect the genes ability to function normally leading to the production
of different types of hemoglobin. A mutation on chromosome 16 in the alpha
globin gene can produce a different hemoglobin such as Constant Spring.
However, mutations in this gene usually lead to the inactivation of the
alpha globin protein production coded by the gene. A mutation can occur
on chromosome 11, affecting one of the beta globins, leading to an abnormal
hemoglobin. Beta globin gene mutations can lead to decreased production
as well as inactivation of the gene. Not all of these mutations have been
defined with DNA analysis, though many of them have and many are constantly
being defined.
There are over 150 known mutations in the beta globin gene, producing
beta thalassemia trait in the heterzygotic individual, and causing a variable
degree of anemia in the homozygote. In addition, there are mutations such
as that leading to hemoglobin E, which do not produce disease even in
the homozygous state. However, hemoglobin E combined with other variant
beta globins can produce mild to severe anemia. Many variant hemoglobins
exist worldwide. Hemoglobins E and S are significant because they can
be co-inherited with thalassemia trait to produce a disease that requires
treatment. Hemoglobin
E is very common among Southeast Asians; California Newborn Screening
Program found that 1 in 12 Southeast Asians, and 1 in 4 Cambodian newborns
had Hgb E trait. Hgb
EE (homozygous) has not been shown to have serious medical implications.
Hgb
E-Beta thalassemia has a wide range of clinical manifestations,
from mild anemia to significant anemia requiring chronic tranfusions.
Hemoglobin S (sickle cell) is prevalent among Africans and African Americans.
Hgb S and beta thalassemia trait can be co-inherited to produce sickle
beta zero (SB0) thalassemia.
The clinical manifestations of this disease resemble Hgb SS disease.
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