Park6

PARK6 is an autosomal recessive young onset familial PD caused by mutations of PINK1 (PTEN-induced kinase 1) (Valente et al. (2001). Clinical features of PARK6 are essentially similar to those of PARK2; the age of onset of the original family studied by Valente et al. (2001) ranged from 32 to 48, somewhat older than those of PARK2. Reflecting this later age of onset, dystonia and sleep benefit which are common to young onset PARK2 are usually not seen in PARK6 unless the age of onset is young.

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S18Y Polymorphism

I93M PD Mutation

Gracile axonal dystrophy mouse

Fig. 4. Schematic presentation of exons of UCH-L1 and its mutations. Only one mutation is known. I93M is associated with autosomal dominant PD. Interestingly homozygous exonic deletion involving exon 7 and 8 induces gracile axonal dystrophy (gad) mouse. S18Y polymorphism is said to confer neuroprotection for sporadic

PD, but controversies exist

Fig. 5. Schematic presentation of exons of PINK1 and its mutations summarized from the following literature, i.e., Valente et al. (2004), Hatano et al. (2004), Heary et al. (2004), Rohe et al. (2004), and Li et al. (2005). As PINK1 is a mitochondrial protein, it has a mitochondria-targeting sequence (exon 1). Two mutations in this targeting sequence are also known. Many missense and nonsense mutations are reported. Recently, we found an exonic deletion involving exon 6 to 8 indicated by the broken line. The solid line indicates the catalytic domain

Fig. 5. Schematic presentation of exons of PINK1 and its mutations summarized from the following literature, i.e., Valente et al. (2004), Hatano et al. (2004), Heary et al. (2004), Rohe et al. (2004), and Li et al. (2005). As PINK1 is a mitochondrial protein, it has a mitochondria-targeting sequence (exon 1). Two mutations in this targeting sequence are also known. Many missense and nonsense mutations are reported. Recently, we found an exonic deletion involving exon 6 to 8 indicated by the broken line. The solid line indicates the catalytic domain

PINK1 has been mapped to the short arm of chromosome 1 at 1p35-p36 (Valente et al., 2004). To date, 17 missense mutations, 3 nonsense mutations, one insertion, and one exon deletion are known (Valente et al., 2004; Hatano et al., 2004; Heary et al., 2004; Rohe et al., 2004; Li et al., 2005) (Fig. 5). We recently found a novel missense mutation (C388R) and an exonic deletion from exon 6 to 8; the latter was the first documented case with exonic deletion mutation in PARK6 (Li et al., 2005). PARK6 appears to be the second most common autosomal recessive PD after PARK2.

PINK1 is a mitochondrial matrix protein and has a protein kinase activity, however, its exact functions are not known. PINK1 stands for PTEN-induced kinase 1. PTEN stands for protein tyrosine phosphatase with homology to tensin: PTEN is a tumor suppressor gene on chromosome 10 mutated in many human tumors (Steck et al., 1997).

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