Özet:
Parkinson's disease (PD) is worldwide the second most common neurodegenerative disorder after Alzheimer's disease. Recently, several genes have been shown to result in PD phenotype. Mutations in these genes may lead to autosomal dominant ( -synuclein, LRRK2), autosomal recessive (Parkin, PINK1, DJ1) or sporadic PD. In the framework of this study, the above five genes were investigated in Turkish patients. For the Parkin gene, we have performed dHPLC analysis prior to sequencing. The high percentage of abnormal dHPLC profiles observed in the patient population revealed only one mutation and 136 polymorphisms. Exon rearrangements were investigated by semi-quantitative multiplex PCR and by MLPA; 12 rearrangements were described in the Parkin gene. PINK1 and DJ1 exons were also sequenced; 75 variations were identified, two being heterozygous mutations. Point mutations in -synuclein are a rare cause of PD and were not found in our patient population. In contrast, triplications and duplications of the whole gene are found more frequently in autosomal dominant forms of the disease. A heterozygous duplication of exons 3 and 4 was described in several patients of a large kindred, and the whole family was subjected to haplotype analysis for chromosome 4q. LRRK2 consists of 51 exons and most mutations are seen in 15 of these. Sequencing of these exons revealed a novel S1508R and a G2019S mutation. G2019S frequency differs among populations and it is associated with three different haplotypes so far. The haplotype of our patient has been shown to have a great homology with the Japanese haplotype. Although an independent origin of the Turkish haplotype cannot be excluded at this point, the huge and centurieslong migration of the Turkic people in Central Asia rather supports a common origin.
