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Gene Review:

PARK3 - Parkinson disease 3 (autosomal dominant,...

Homo sapiens

DeStefano, A.L. et al., Lockhart, P.J. et al., Grimes, D.A. et al., West, A.B. et al., Karamohamed, S. et al., et al.

Hattori, Kobayashi, Sasaki-Hatano, Sato, Mizuno, Karamohamed, DeStefano, Wilk, Shoemaker, Golbe, Mark, Lazzarini, Suchowersky, Labelle, Guttman, Currie, Wooten, Stacy, Saint-Hilaire, Feldman, Sullivan, Xu, Watts, Growdon, Lew, Waters, Vieregge, Pramstaller, Klein, Racette, Perlmutter, Parsian, Singer, Montgomery, Baker, Gusella, Fink, Myers, Herbert, Grimes, Grimes, Racacho, Scoggan, Han, Schwarz, Woulfe, Bulman, DeStefano, Lew, Golbe, Mark, Lazzarini, Guttman, Montgomery, Waters, Singer, Watts, Currie, Wooten, Maher, Wilk, Sullivan, Slater, Saint-Hilaire, Feldman, Suchowersky, Lafontaine, Labelle, Growdon, Vieregge, Pramstaller, Klein, Hubble, Reider, Stacy, MacDonald, Gusella, Myers,

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Disease relevance of PARK3

PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study [1].

High impact information on PARK3

This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD [1].
Sequence analysis of 2p13 linked individuals affected with PD did not reveal any potentially pathogenic mutations within SFXN5, suggesting SFXN5 does not correspond to PARK3 [2].
Previously we mapped a susceptibility gene for an autosomal dominant form of PD to a 10.6 cM region of chromosome 2p (PARK3; OMIM 602404) [2].
The genes described here are positional candidates for the Parkinson disease susceptibility locus PARK3 that was recently mapped to the corresponding region of human chromosome band 2p13.1 [3].
Now, a total of five causative genes including NR4A2 have been identified, and others such as PARK3, -4, -6, -8, -9, -10 have been mapped as hereditary forms of familial PD [4].

Biological context of PARK3

Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes [5].
METHODS: Single nucleotide polymorphisms (SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families [6].

Anatomical context of PARK3

A susceptibility gene for Parkinson's disease (PD) with late onset and typical Lewy-body pathology maps to chromosome 2p13 (PARK3) [7].

Other interactions of PARK3

The alpha-synuclein(4q21.3-23), Parkin(6q25.2-27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase-L1 (4p14-16.3) and PARK6 and PARK7 (1p35-36) loci were excluded in this kindred using closely linked markers [8].
The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations [9].

Analytical, diagnostic and therapeutic context of PARK3

Here we report progress in the refinement of the PARK3 locus and sequence analysis of candidate genes within the region [5].

References

PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study. DeStefano, A.L., Lew, M.F., Golbe, L.I., Mark, M.H., Lazzarini, A.M., Guttman, M., Montgomery, E., Waters, C.H., Singer, C., Watts, R.L., Currie, L.J., Wooten, G.F., Maher, N.E., Wilk, J.B., Sullivan, K.M., Slater, K.M., Saint-Hilaire, M.H., Feldman, R.G., Suchowersky, O., Lafontaine, A.L., Labelle, N., Growdon, J.H., Vieregge, P., Pramstaller, P.P., Klein, C., Hubble, J.P., Reider, C.R., Stacy, M., MacDonald, M.E., Gusella, J.F., Myers, R.H. Am. J. Hum. Genet. (2002) [Pubmed]
The human sideroflexin 5 (SFXN5) gene: sequence, expression analysis and exclusion as a candidate for PARK3. Lockhart, P.J., Holtom, B., Lincoln, S., Hussey, J., Zimprich, A., Gasser, T., Wszolek, Z.K., Hardy, J., Farrer, M.J. Gene (2002) [Pubmed]
High-resolution genetic, physical, and transcript map of the mnd2 region of mouse chromosome 6. Weber, J.S., Jang, W., Simin, K., Lu, W., Yu, J., Meisler, M.H. Genomics (1998) [Pubmed]
Familial Parkinson's disease: a hint to elucidate the mechanisms of nigral degeneration. Hattori, N., Kobayashi, H., Sasaki-Hatano, Y., Sato, K., Mizuno, Y. J. Neurol. (2003) [Pubmed]
Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes. West, A.B., Zimprich, A., Lockhart, P.J., Farrer, M., Singleton, A., Holtom, B., Lincoln, S., Hofer, A., Hill, L., Müller-Myhsok, B., Wszolek, Z.K., Hardy, J., Gasser, T. Eur. J. Hum. Genet. (2001) [Pubmed]
A haplotype at the PARK3 locus influences onset age for Parkinson's disease: the GenePD study. Karamohamed, S., DeStefano, A.L., Wilk, J.B., Shoemaker, C.M., Golbe, L.I., Mark, M.H., Lazzarini, A.M., Suchowersky, O., Labelle, N., Guttman, M., Currie, L.J., Wooten, G.F., Stacy, M., Saint-Hilaire, M., Feldman, R.G., Sullivan, K.M., Xu, G., Watts, R., Growdon, J., Lew, M., Waters, C., Vieregge, P., Pramstaller, P.P., Klein, C., Racette, B.A., Perlmutter, J.S., Parsian, A., Singer, C., Montgomery, E., Baker, K., Gusella, J.F., Fink, S.J., Myers, R.H., Herbert, A. Neurology (2003) [Pubmed]
Autosomal-dominant Parkinson's disease linked to 2p13 is not caused by mutations in transforming growth factor alpha (TGF alpha) (short communication). Zink, M., Grim, L., Wszolek, Z.K., Gasser, T. Journal of neural transmission (Vienna, Austria : 1996) (2001) [Pubmed]
Large French-Canadian family with Lewy body parkinsonism: exclusion of known loci. Grimes, D.A., Grimes, J.D., Racacho, L., Scoggan, K.A., Han, F., Schwarz, B.A., Woulfe, J., Bulman, D. Mov. Disord. (2002) [Pubmed]
The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations. Sharma, M., Mueller, J.C., Zimprich, A., Lichtner, P., Hofer, A., Leitner, P., Maass, S., Berg, D., Dürr, A., Bonifati, V., De Michele, G., Oostra, B., Brice, A., Wood, N.W., Muller-Myhsok, B., Gasser, T. J. Med. Genet. (2006) [Pubmed]

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