Review of:
Mutations in Severe Combined Immune Deficiency (SCID) Due to JAK3 Deficiency
Notarangelo, et al.
Human Mutation 18:255-263 (2001)
Human Mutation 18:255-263 (2001)
Severe combined immunodeficiency disease or SCID is a
devastating disease that presents in about 1 out of every 50,000 infants at
birth. This disease is characterized by
the lack of a functional immune system, and is fatal without a bone marrow
transplant. The disease is caused by DNA
mutations which can occur in a variety of locations with the second
most common cause of SCID being mutations inside the JAK3 (Janus Kinase 3) gene.
The JAK3 gene produces the JAK3 protein which functions primarily inside of the cells that constitute blood. The protein works together with multiple other proteins as one of a series of steps that are necessary to produce and stabilize the cells that make up the human immune system. Proteins can be imagined as wires that are coiled, looped and folded into specific shapes; they contain segments, called “domains”, that are important for the different interactions the protein must have with its environment in order to work properly. Notarangelo et al. collected data from various researchers which showed that the DNA mutations which cause SCID can affect all four of the domains in the JAK3 protein.
SCID is a recessive disease. In the case of the JAK3 gene this means that both copies of the gene (genes in humans for the most part come in pairs) must be mutated in order for a person to have SCID. This paper presents research showing that children who are born with certain types of mutations in both copies of the gene can have SCID that is not as severe as children with other mutations. If the mutations a child has in both genes are different, they will likely produce two different kinds of mutated JAK3 proteins, and in children who are diagnosed with SCID relatively late in life at least one of those mutated proteins may work just well enough to allow them to have a very weak rather than completely absent immune system.
By studying children who have SCID researchers can learn more about the disease and the mutations that cause it. Gene therapy is a potential future treatment option for children with the disease, but SCID research is ongoing.
The JAK3 gene produces the JAK3 protein which functions primarily inside of the cells that constitute blood. The protein works together with multiple other proteins as one of a series of steps that are necessary to produce and stabilize the cells that make up the human immune system. Proteins can be imagined as wires that are coiled, looped and folded into specific shapes; they contain segments, called “domains”, that are important for the different interactions the protein must have with its environment in order to work properly. Notarangelo et al. collected data from various researchers which showed that the DNA mutations which cause SCID can affect all four of the domains in the JAK3 protein.
SCID is a recessive disease. In the case of the JAK3 gene this means that both copies of the gene (genes in humans for the most part come in pairs) must be mutated in order for a person to have SCID. This paper presents research showing that children who are born with certain types of mutations in both copies of the gene can have SCID that is not as severe as children with other mutations. If the mutations a child has in both genes are different, they will likely produce two different kinds of mutated JAK3 proteins, and in children who are diagnosed with SCID relatively late in life at least one of those mutated proteins may work just well enough to allow them to have a very weak rather than completely absent immune system.
By studying children who have SCID researchers can learn more about the disease and the mutations that cause it. Gene therapy is a potential future treatment option for children with the disease, but SCID research is ongoing.
This article can be accessed online here [1].
References
[1] Notarangelo, L.D., Mella, P., Jones, A., de Saint Basile, G., Savoldi, G., Cranston, T., Vihinen, M., Schumacher, R.F. (2001). Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency. Human Mutation, 18(4):255–63. doi: 10.1002/humu.1188
