by Amy Pack
There are many blood disorders known to man. They affect people in different
ways and have numerous different symptoms. Rheumatoid Arthritis, cellulitis,
and frequent pneumonia are just a few symptoms of having a blood disorder.
Blood disorders are usually cause by a mutation in a biochemical pathway.
Most blood disorders are passed on from generation to generation. For example,
von Willebrand Disease can be passed to the offspring from genes on autosomal
chromosomes, or disorders can be passed from one of the sex chromosomes
(like hemophilia). Von Willebrand disease is the most common inherited bleeding
disorder to humans. Von Willebrand disease affects males and females alike,
while hemophilia usually affects males. C2 deficiency is another blood disorder
that affects humans. In this case study we will look at what causes this
disorder and how it is passed on to offspring.
C2 deficiency is a genetic disease occurring mainly in Caucasians. It is
a disease that affects males and females alike. People with this deficiency
lack functional and immunological C2 protein. C2 deficiency is a inherited
disorder passed from parent to offspring. This mode of inheritance for C2
deficiency is autosomal recessive. This deficiency can be passed to offspring
as a heterozygous or a homozygous trait. The difference in these two are
the severity of the symptoms. If a person is homozygous the C2 deficiency
will be more penetrant. If it is displayed as a homozygous trait each parent
must be carrying the mutation or show some symptoms of having this disorder.
If it is passed as a heterozygous trait one parent must be carrying the
mutation in there genome. Individuals who exhibit this deficiency, or other
protein deficiencies are highly susceptible to infection. Children carrying
this gene mutation are more susceptible to bacterial infection then the
The C2 gene is located on chromosome 6. It has been proven that individuals
that are homozygous for these protein mutations have low natural killer
Alper et al. (1994). This means that these people have lower immune system
than normal and are more susceptible to infection. This gene encodes for
the C2 protein which is part of an immune system biochemical pathway called
the complement system. It has been proposed that genetic change in the C2
gene has a way of altering the immune regulation mechanism Alper et al.
(1994).. Disrupting the immune biochemical pathway causes autoimmune diseases.
This deficiency has been proven to be have a multifactorial trait. Studies
have shown that unrelated people with this deficiency show symptoms of lupus
erythematosus and polyarteritis. C2 deficiency is often complicated by immunological
disorders such as systemic lupus erythematosis. C2 deficiency has rarely
been reported in the Japanese population. There was a case that was reported
in the Japanese population that helped prove this disorder is associated
with other deficiencies. It has been associated with C9 deficiency and chronic
idiopathic neutropenia Merralls (1995). C9 deficiency has been found to
appear in 0.086% of the Japanese population who are found to have immune,
viral and infectious diseases Merralls (1995). It has not been proven that
these disorders are linked together, but it is highly suggested that the
C9 deficiency has cause some type of mutation on the C2 gene , showing that
there is a relationship among them Merralls (1995).
In Caucasians C2 deficiency is frequently associated with systemic lupus
erythematosis, vasculitis, ankylosing spondylitis, and diabetes. The frequency
of homozygous C2 deficiency in patients with rheumatologic disease is about
0.2% more common than that in the general U.S. population
On a molecular level C2 deficiency is caused by a mutation in the C2 gene
expression. When this defect has taken place there is no detectable mRNA
formed Johnson et al. (1992). In a person who is heterozygous for this deficiency
there is a reduced amount of C2 mRNA Johnson et al. (1992). There are two
main types of C2 deficiency.
Type I and type II are characterized by different expressions and deletions
of the gene. Type I is characterized by no detectable C2 protein being synthesized.
There is a deletion in the 134 basepair single exon Johnson et al. (1992).
Exons are the part of the gene that are expressed, and the intron are the
part that are cut out. This deletion causes a frame shift in the chromosome.
The result of this shift is the generation of a termination codon, TGA,
16 basepairs downstream from the deletion Johnson et al. (1992). A 28 basepair
deletion is detected in the gene 9 basepairs from the 3-prime end of the
134 basepair exon. Type II has a lower than normal synthesis of the C2 protein
Johnson et al. (1992). There are two mutation detected in this type, they
are on exon 5 and exon 11 Johnson et al. (1992).
In conclusion, C2 deficiency is a disorder cause by a mutation in chromosome
6. This mutation causes impaired immunity against bacterial infection. A
person homozygous for C2 deficiency will have a more sever case of infections
than a person who is heterozygous for this deficiency. This deficiency is
a multifactorial trait that is often associated with other immune deficiencies.
Duby DP. Alper CA,;
Polymorphic Hh genes in the HLA-B© region control natural killer cell
frequency and activity Journal of Experimental medicine, 179 (4):1193-203,
1994 Apr 1.
Johnson, C.A.; Densen, P.; Hurford, R.K., Jr.; Colten, H.R.; Wetse, R.A.;
Type I human complement C2 deficiency: a 28-base pair gene deletion causes
skipping of exon 6 during RNA spicing, 1992.
Merralls, Stephanie.; Complement Deficiencies, 1995.
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