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Parkinson's disease (PD) is a common neurodegenerative syndrome with age-related prevalence. Generally PD is considered a sporadic illness but ~14% (range 10-30%) of patients have one or more 1st degree relatives with parkinsonism. Recent studies have implicated at least 13 PARK loci in disease pathogenesis. In recent years, several monogenetic causes of parkinsonism have been identified including dominant mutations in alpha-synuclein () and leucine-rich repeat kinase 2 (; Lrrk2), and recessive mutations in parkin (), Pteninduced kinase 1 (), DJ-1 () and A2.
We performed prospective clinical, epidemiological and genetic study of Parkinsonism in Tunisia.Tis study concerned in total, 1212 structured interviews, clinical examination and blood samples were carried out including 240 patients with idiopathic PD, 91 probands with familial parkinsonism (defined as having one or more affected individuals with 1-3º of blood relationship) and 368 control subjects. Of the 91 probands, 63 kindreds, each containing 2 or more affected individuals, were successfully recruited to include a total of 210 affected and 245 unaffected family members. The 63 kindreds were subsequently genotyped by with 1100 microsatellite markers for linkage analysis.
In familial cases Lrrk2 G2019S mutation was found as the cause of parkinsonism in 34/80 (42%) kindreds including 21homozygous patients.In addition this mutation was found the cause of parkinsonism in 30% of l patients without known familial history. There were no significant differences in various clinical parameters between and idiopathic PD, although LRRK2 patients seemed to develop less dementia and more motor dyskenesia. The clinical phenotypes in homozygous and heterozygous Lrrk2 G2019S carriers were comparable.
Disease penetrance in Lrrk2 G2019S carriers ranges from ~20% in those younger than 50 years to greater than 80% at 80 years .mutations were rare but homozygous inheritance of mutations was found responsible pof PD in d 14% of kindreds with familial parkinsonism. Homozygous and compound heterozygous mutations in and are most frequently observed in early-onset Parkinsonism in Asians and Caucasians The most apparent difference between LLRK2 and was the younger age at onset in homozygous individuals, with an akinetic-rigid presentation without evidence of subsequent cognitive decline or dementia
Conclusion
Parkinson disease displays a high frequency of genetic forms in Tunisia with in particular a large predominance of G2019S mutation .This gives an opportunity for a detailed phenotypic analysis and gene penetrance study. Comparative genetic studies in the other African countries may help the understanding of the causes of this particular distribution of Parkinsonism in Tunisia |
