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GENETIC CAUSES OF PARKINSON'S DISEASE

 
 
 

INHERITED v ACQUIRED

Genetic disorders are usually inherited. However, if somebody has relatives with the same medical disorder it does not mean that it has been inherited. People within the same family can share the same medical disorder because they have similar environmental factors. Genetic disorders can also be acquired in people that have no relatives with that genetic disorder. So the fact that somebody does or does not have relatives with the same medical disorder is no guide to whether their medical disorder is genetic. Nobody really knows whether or not their medical disorder is genetic until it is specifically tested.


GENETIC ERROR

Genetic disorders usually have effect due to the the faulty formation of proteins. Proteins are essential for the body to carry out virtually all biological functions in the body. Enzymes are one type of protein that facilitate biochemical reactions in the body. Some hormones are proteins that stimulate or reduce biochemical functions.

Proteins are a chain of amino acids just like pearl necklaces are a chain of pearls, such as in the following example : Tyr-Ser-Phe-Pro-Cys-Thr

When there is a genetic disorder, instead of producing the above example, the following faulty version may be produced instead :Tyr-Ser-Phe-Glu-Cys-Thr

One amino acid, in this case Proline (Pro), is replaced by another amino instead, in this case Glutamic Acid (Glu).


EFFECTS OF GENETIC DISORDERS

Although there is often not much difference in the faulty protein that is formed, this can be enough to bring a biochemical function to a complete halt.

Some genetic disorders can cease a biochemical function completely, from birth until death. Soome genetic disorders will make a medical disorder more likely but not inevitable. Some genetic disorders will cause no problem at all.

Judging from the faults caused by genetic Parkinson's Disease, it appears likely that somebody will either be more inclined to develop Parkinson's Disease, or for Parkinson's Disease to have more effect when it is developed. In theory at least it does not appear as if causes Parkinson's Disease inevitably or irreversibly.


FAULTY GENES

Those fault genes know to affect Parkinson's Disease are : PARK 2 (Parkin), PARK 6 (PINK 1), PARK 7 (DJ-1), SNCA, LRRK2, UCHL1, SNCAIP, GBA, NR4A2, CYP2D6, PARK 3; PARK 4, PARK 8, PARK 10 and PARK 11.
PARK1 (OMIM #168601), caused by mutations in the SNCA gene, which codes for the protein alpha-synuclein. PARK1 causes autosomal dominant Parkinson disease. So-called PARK4 is probably caused by triplication of SNCA.

PARK2 (OMIM #602544), caused by mutations in protein parkin. Parkin mutations may be one of the most common known genetic causes of early-onset Parkinson disease. In one study, of patients with onset of Parkinson disease prior to age 40 (10% of all PD patients), 18% had parkin mutations, with 5% homozygous mutations.[12] Patients with an autosomal recessive family history of parkinsonism are much more likely to carry parkin mutations if age at onset is less than 20 (80% vs. 28% with onset over age 40). Patients with parkin mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.

PARK3 (OMIM #602404), mapped to 2p, autosomal dominant, only described in a few kindreds.

PARK5, caused by mutations in the UCHL1 gene (OMIM #191342) which codes for the protein ubiquitin carboxy-terminal hydrolase L1

PARK6 (OMIM #605909), caused by mutations in PINK1 (OMIM #608309) which codes for the protein PTEN-induced putative kinase 1.

PARK7 (OMIM #606324), caused by mutations in DJ-1 (OMIM #602533)

PARK8 (OMIM #607060), caused by mutations in LRRK2 which codes for the protein dardarin. In vitro, mutant LRRK2 causes protein aggregation and cell death, possibly through an interaction with parkin.[14] LRRK2 mutations, of which the most common is G2019S, cause autosomal dominant Parkinson disease, with a penetrance of nearly 100% by age 80.[15] G2019S is the most common known genetic cause of Parkinson disease, found in 1-6% of U.S. and European PD patients.[16] It is especially common in Ashkenazi Jewish patients, with a prevalence of 29.7% in familial cases and 13.3% in sporadic.

PARK12 (OMIM #300557), maps to the X chromosome

 

 

 

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