C2 Deficiency
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 general public.

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 activity
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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