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The official name of this gene is “sepiapterin reductase (7,8-dihydrobiopterin:NADP+ oxidoreductase).”
SPR is the gene's official symbol. The SPR gene is also known by other names, listed below.
The SPR gene provides instructions for making the sepiapterin reductase enzyme. This enzyme is involved in the last of three steps in the production of a molecule called tetrahydrobiopterin (BH4). Other enzymes help carry out the first and second steps in this process. The sepiapterin reductase enzyme converts a molecule called 6-pyruvoyl-tetrahydropterin to tetrahydrobiopterin. Tetrahydrobiopterin helps process several building blocks of proteins (amino acids), and is involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Specifically, tetrahydrobiopterin is involved in the production of two neurotransmitters called dopamine and serotonin. Among their many functions, dopamine transmits signals within the brain to produce smooth physical movements, and serotonin regulates mood, emotion, sleep, and appetite.
The SPR gene belongs to a family of genes called SDR (short chain dehydrogenase/reductase superfamily).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
At least four mutations in the SPR gene have been found to cause dopa-responsive dystonia. This condition is characterized by a pattern of involuntary muscle contractions (dystonia), tremors, and other uncontrolled movements and usually responds to treatment with a medication called L-Dopa. Dopa-responsive dystonia can be caused by mutations in one copy or both copies of the SPR gene in each cell. These mutations lead to the production of a sepiapterin reductase enzyme with reduced or absent function. In most parts of the body, there are alternate pathways that do not use sepiapterin reductase for the production of tetrahydrobiopterin, but these processes do not occur in the brain. Therefore, people with sepiapterin reductase deficiency have a lack of tetrahydrobiopterin in the brain, which affects the production of dopamine and serotonin. The lack of these two neurotransmitters causes the movement problems and other characteristic features of dopa-responsive dystonia.
More than a dozen mutations in the SPR gene have been found to cause sepiapterin reductase deficiency, a condition characterized by progressive problems with movement. Sepiapterin reductase deficiency results when two copies of the SPR gene are mutated in each cell. These mutations include changes that replace amino acids; alter the way the gene's instructions are pieced together to produce the enzyme; or result in a shortened, nonfunctional enzyme. All these mutations lead to the production of enzymes with reduced or no function. A common mutation in affected individuals that replaces the amino acid arginine with the amino acid glycine at position 150 in the enzyme (written as Arg150Gly or R150G) prevents the production of any sepiapterin reductase.
SPR gene mutations disrupt the production of sepiapterin reductase. Most SPR gene mutations result in an enzyme with little or no function. A nonfunctional sepiapterin reductase leads to a lack of tetrahydrobiopterin and a decrease in the production of dopamine and serotonin in the brain. The shortage of these neurotransmitters causes the movement abnormalities and other features of sepiapterin reductase deficiency.
Sepiapterin reductase deficiency is more severe than dopa-responsive dystonia likely because both copies of the SPR gene are mutated, which leads to a more severe enzyme shortage than in dopa-responsive dystonia, in which only one copy of the gene has a mutation.
Cytogenetic Location: 2p14-p12
Molecular Location on chromosome 2: base pairs 73,114,511 to 73,119,288
The SPR gene is located on the short (p) arm of chromosome 2 between positions 14 and 12.
More precisely, the SPR gene is located from base pair 73,114,511 to base pair 73,119,288 on chromosome 2.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about SPR helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; amino acid ; cell ; deficiency ; dehydrogenase ; dopamine ; dystonia ; enzyme ; gene ; glycine ; involuntary ; molecule ; mutation ; neurotransmitters ; oxidoreductase ; phenylalanine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.