MedGen

A functional anomaly of mitochondria. [from HPO]

Parkin type of early-onset Parkinson disease (PARK-Parkin) is characterized by the cardinal signs of Parkinson disease (PD): bradykinesia, resting tremor, and rigidity. The median age at onset is 31 years (range: 3-81 years). The disease is slowly progressive: disease duration of more than 50 years has been reported. Clinical findings vary; hyperreflexia is common. Lower-limb dystonia may be a presenting sign and cognitive decline appears to be no more frequent than in the general population. Dyskinesia as a result of treatment with levodopa frequently occurs. [from GeneReviews]

A neurodegenerative disease that is characterized by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibers or glial cells. [url:http://en.wikipedia.org/wiki/Synucleinopathies ] [from MONDO]

Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait. [from HPO]

Parkinson disease (PD) was first described by James Parkinson in 1817. It is the second most common neurodegenerative disorder after Alzheimer disease (AD; 104300), affecting approximately 1% of the population over age 50 (Polymeropoulos et al., 1996). Reviews Warner and Schapira (2003) reviewed the genetic and environmental causes of Parkinson disease. Feany (2004) reviewed the genetics of Parkinson disease and provided a speculative model of interactions among proteins implicated in PD. Lees et al. (2009) provided a review of Parkinson disease, with emphasis on diagnosis, neuropathology, and treatment. Genetic Heterogeneity of Parkinson Disease Several loci for autosomal dominant Parkinson disease have been identified, including PARK1 (168601) and PARK4, caused by mutation in or triplication of the alpha-synuclein gene (SNCA; 163890), respectively, on 4q22; PARK5 (191342), caused by mutation in the UCHL1 gene on 4p13; PARK8 (607060), caused by mutation in the LRRK2 gene (609007) on 12q12; PARK11 (607688), caused by mutation in the GIGYF2 gene (612003) on 2q37; PARK13 (610297), caused by mutation in the HTRA2 gene (606441) on 2p13; PARK17 (614203), caused by mutation in the VPS35 gene (601501) on 16q11; PARK18 (614251), caused by mutation in the EIF4G1 gene (600495) on 3q27; PARK22 (616710), caused by mutation in the CHCHD2 gene (616244) on 7p11; PARK24 (619491), caused by mutation in the PSAP gene (176801) on 10q22; and PARK26 (620923), caused by mutation in the RAB32 gene (612906) on chromosome 6q24. Several loci for autosomal recessive early-onset Parkinson disease have been identified: PARK2 (600116), caused by mutation in the gene encoding parkin (PRKN, PARK2; 602544) on 6q26; PARK6 (605909), caused by mutation in the PINK1 gene (608309) on 1p36; PARK7 (606324), caused by mutation in the DJ1 gene (PARK7; 602533) on 1p36; PARK14 (612953), caused by mutation in the PLA2G6 gene (603604) on 22q13; PARK15 (260300), caused by mutation in the FBXO7 gene (605648) on 22q12.3; PARK19A (615528) and PARK19B (see 615528), caused by mutation in the DNAJC6 gene (608375) on 1p31.3; PARK20 (615530), caused by mutation in the SYNJ1 gene (604297) on 21q22; and PARK23 (616840), caused by mutation in the VPS13C gene (608879) on 15q22; and PARK25 (620482), caused by mutation in the PTPA gene (600756) on 9q34. PARK3 (602404) has been mapped to chromosome 2p13; PARK10 (606852) has been mapped to chromosome 1p32; PARK16 (613164) has been mapped to chromosome 1q32. See also PARK21 (616361). A locus on the X chromosome has been identified (PARK12; 300557). There is also evidence that mitochondrial mutations may cause or contribute to Parkinson disease (see 556500). Susceptibility to the development of the more common late-onset form of Parkinson disease has been associated with polymorphisms or mutations in several genes, including GBA (606463), MAPT (157140), MC1R (155555), ADH1C (103730), and genes at the HLA locus (see, e.g., HLA-DRA, 142860). Each of these risk factors independently may have a modest effect on disease development, but together may have a substantial cumulative effect (Hamza et al., 2010). Susceptibility to PD may also be conferred by expanded trinucleotide repeats in several genes causing other neurologic disorders usually characterized by spinocerebellar ataxia (SCA), including the ATXN2 (601517), ATXN3 (607047), TBP (600075), and ATXN8OS (603680) genes. [from OMIM]

PINK1 type of young-onset Parkinson disease is characterized by early onset (mean age 33 years) of tremor, bradykinesia, and rigidity that are often indistinguishable from other causes of Parkinson disease. Lower-limb dystonia may be a presenting sign. Postural instability, hyperreflexia, abnormal behavior, and psychiatric manifestations have been described. The disease is usually slowly progressive. Individuals have a marked and sustained response to oral administration of levodopa (L-dopa), frequently associated with L-dopa-induced fluctuations and dyskinesias. [from GeneReviews]