The Incidence of Mutation on the Leucine-rich Repeat Kinase 2 Gene in Patients with Parkinson’s Disease in Slovakia

Czech version

Authors: K. Kračunová ¹; M. Kovačovicová ²; M. Baldovič ²; P. Valkovič ^3,4; Ľ. Kádaši ²; J. Benetin ¹
Authors‘ workplace: Neurologická klinika SZU a UN Bratislava ¹; Katedra molekulárnej biológie PriF UK v Bratislave ²; II. Neurologická klinika LF UK a UN Bratislava ³; Ústav normálnej a patologickej fyziológie SAV, Bratislava ⁴
Published in: Cesk Slov Neurol N 2011; 74/107(4): 443-445
Category: Original Paper

Overview

Introduction:
The objective of this study was to determine the prevalence of LRRK2gene mutations in Slovak PD patients. Patients and methods: 126 PD patients (78 men, 48 women) were included in the study. The average age of this population was 57 years. Twenty-four patients (19.1%) reported a positive family history of parkinsonism; Hoehn-Yahr stage was between 1 and 5 (mean 2.6). There were 19 patients with early-onset parkinsonism (beginning before the age of 45) in the group. All subjects were screened for selected exons in the LRRK2 gene by means of dHPLC analysis. Exons 31, 35, 41 and 48 we examined. Results: From a total of 126 samples, one exonic and four intronic polymorphisms in the exon 48 and one intronic polymorphism in exon 35 of the LRRK2 gene were detected. No common pathogenic mutations were found. Conclusion: The study indicates that the most common mutations in the LRRK2 gene do not play an important role in the aetiology of Parkinson’s disease in central Europe. This has also been shown by previous studies. It must be emphasized that the overall sample size is relatively small, particularly for the familial PD cases.

Key words:
Parkinson´s disease – genetics – LRRK2 – mutation – polymorphism

Sources

1. Lohmann K, Klein C. Genetics of Parkinson’s disease. Continuum: lifelong learning in neurology. Neurogenetics 2008; 14(2): 90–113.

2. Gasser T. Update on the genetics of Parkinson’s disease. Mov Disord 2007; 22 (Suppl 17): S343–S350.

3. Fiala O, Růžička E. Genetika Parkinsonovy nemoci. Cesk Slov Neurol N 2009; 72/105(5): 419–428.

4. Wider C, Wszolek ZK. Clinical genetics of Parkinson’s disease and related disorders. Parkinsonism Relat Disord 2007; 13 (Suppl 3): S229–S232.

5. Bonifati V. Genetics of Parkinsonism. Parkinsonism Relat Disord 2007; 13 (Suppl 3): S233–S241.

6. Farrer MJ. Genetics of Parkinson’s disease, paradigm shifts and future prospects. Nat Rev Genet 2006; 7(4): 306–318.

7. Paisan-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J,van der Brug M et al. Cloning of the gene containing mutations that cause PARK 8-linked Parkinson’s disease. Neuron 2004; 44(4): 601–607.

8. Di Fonzo A, Wu-Chou YH, Lu CS, van Doeselaar M, Simons EJ, Rohé CF et al. A common missense variant in the LRRK 2 gene, Gly2385Arg, associated with Parkinson’s disease in Taiwan. Neurogenetics 2006; 7(3): 133–138.

9. Ross OA, Wu YR, Lee MC, Funayama M, Chen ML, Soto AI et al. Analysis of LRRK2 R1628P as a risk factor for Parkinson‘s disease. Ann Neurol 2008; 64(1): 88–92.

10. Nichols WC, Pankratz N, Hernandez D, Paisan-Ruiz C, Jain S, Halter CA et al. Genetic screening for a single common LRRK 2 mutation in familial Parkinson’s disease. Lancet 2005; 365(9457): 410–412.

11. Di Fonzo A, Rohé CF, Ferreira J, Chien HF, Vacca L, Stocci F et al. A frequent LRRK 2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet 2005; 365(9457): 412–415.

12. Gilks WP, Abou Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K et al. A common LRRK 2 mutation in idiopathic Parkinson’s disease. Lancet 2005; 365(9457): 415–416.

13. Lasage S, Dürr A, Brice A. LRRK 2 – gène majeur de la maladie de Parkinson dans les pays du Magreb. Med Sci (Paris) 2006; 22(5): 470–471.

14. Ozelius LJ, Senthil G, Saunders Pulman R, Ohmann E, Deligtisch A, Tagliati M et al. LRRK 2 G2019S as a cause of Parkinson’s disease in Ashkenasi Jews. New Engl J Med 2006; 354(4): 424–425.

15. Ferreira JJ, Guedes LC, Rosa MM, Coelho M, van Doeselaar M, Schweiger D. High prevalence of LRRK 2 mutations in familial and sporadic Parkinson’s disease in Portugal. Mov Disord 2007; 22(8): 1194–1201.

16. Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J et al. Identification of a novel LRRK 2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet 2005; 76(4): 672–680.

17. Haubenberger D, Bonelli S, Hotzy C, Leitner P, Lichtner P, Samal D et al. A novel LRRK 2 mutation in an Austrian cohort of patients with Parkinson’s disease. Mov Disord 2007; 22(11): 1640–1643.

18. Bialecka M, Hui S, Klodowska-Duda G, Opala G, Tan EK, Drozdik M. Analysis of LRRK 2 G2019S and I2020T mutations in Parkinson’s disease. Neurosci Lett 2005; 390(1): 1–3.

19. Fiala O, Pospisilova L, Prochazkova J, Matejckova M, Martasek P, Novaková L et al. Parkin mutations and phenotypic features in Czech patients with early-onset Parkinson’s disease. Neuro Endocrinol Lett 2010; 31(2): 187–192.

20. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004; 44: 601–607.

21. Khan NL, Jain S, Lynch JM, Pavese N, bou-Sleiman P, Holton JL et al. Mutations in the gene LRRK2 encoding dardarin (PARK8) cause familial Parkinson‘s disease: clinical, pathological, olfactory and functional imaging and genetic data. Brain 2005; 128: 2786–2796.