tailieunhanh - Parkinson’s Disease Methods and Protocols

Idiopathic Parkinson’s disease (PD) is an age-dependent, neurodegenerative disorder and is predominantly sporadic. Only 20–30% of patients have a positive family history for PD with a complex mode of inheritance. In a few extended families, the disease is inherited as an autosomal dominant trait. Linkage to chromosome 4 was reported in a large Italian kindred multiply affected by an early-onset form of PD (1). However, this finding was not replicated in a sample of 94 Caucasian families by Scott et al. (2), or in 13 multigenerational families by Gasser et al. (3) | 1 Point Mutations in the a-Synuclein Gene Abbas Parsian and Joel S. Perlmutter 1. Introduction Idiopathic Parkinson s disease PD is an age-dependent neurodegenerative disorder and is predominantly sporadic. Only 20-30 of patients have a positive family history for PD with a complex mode of inheritance. In a few extended families the disease is inherited as an autosomal dominant trait. Linkage to chromosome 4 was reported in a large Italian kindred multiply affected by an early-onset form of PD 1 . However this finding was not replicated in a sample of 94 Caucasian families by Scott et al. 2 or in 13 multigenerational families by Gasser et al. 3 . It has recently been demonstrated that a mutation within the a-synuclein gene on chromosome 4 segregates with disease in the Italian family 4 . It was further demonstrated that the same missense mutation was also present in three Greek families with early onset PD. Sequence analysis of exon 4 of the gene revealed a single base pair change at position 209 from G to A G209A . This mutation results in an Ala to Thr substitution at position 53 of the protein Ala53Thr and creates a Tsp45I restriction site 4 . This is the first report of a mutation causing clinically and pathologically defined idiopathic PD associated with the critical pathologic finding the intraneuronal inclusions called Lewy bodies in brainstem nuclei including the substantia nigra. However Kruger et al. 5 reported a G C transversion at position 88 of the coding sequence in two sibs and the deceased mother in a German family. It was concluded that this mutation is the cause of PD in this family. More recently Papadimitriou et al. 6 reported two additional Greek families with autosomal dominant PD associated with the G209A mutation in the a-synuclein gene. These families are clinically similar to other PD families with the mutation in the a-synuclein gene since they also have early onset infrequent resting tremor relatively rapid progression and excellent .