Ahmet ADIGUZEL, Sibel ALTINAYAR, Gonca GÜLBAY, Elif YESİLADA

LRRK2 G2019S, I2020T, R1441C GENE mutation analysis in patients with idiopathic Parkinson’s in Turkey

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The number of genetic studies on the etiopathogenesis of the disease has increased in the recent years. Leucine-rich repeat kinase 2 (LRRK2) gene mutation is the most common in autosomal dominant and sporadic PD. In this study, we aim to investigate the LRRK2 mutation frequency in patients diagnosed with idiopathic PD in and around Malatya province in eastern Turkey and to determine certain parameters in positive cases such as phenotype characteristics and treatment efficacy. A total of 170 patients (106 male and 64 female) were included. The most common loci of the LRRK2 gene (G2019S, I2020T and R1441C) were examined. To identify mutations, genotyping studies were performed by targeting related gene regions in isolated DNA using real-time polymerase chain reaction. No mutation was detected in any patient. Therefore, the probability of G2019S, I2020T and R1441C point mutations in the LRRK2 gene was very low in PD patients in Malatya region, which is a region of Turkey closer to the Middle East. Future studies investigating mutations involved in other loci of the LRRK2 gene with larger sample size in a wider geography in Turkey will provide more information about the genotype–phenotype relationship, incidence and carrier characteristics.

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1. Martinez-Martin P. The importance of non-motor disturbances to quality of life in Parkinson’s disease. J Neurol Sci. 2011;310:12-6.

2. Lill CM. Genetics of Parkinson’s disease. Mol Cell Probes. 2016;30-6:386- 96.

3. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124-8:901-5.

4. Funayama M, Hasegawa K, Kowa H, et al. A new locus for Parkinson’s disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol. 2002;51- 3:296-301.

5. Healy DG, Falchi M, O’Sullivan SS, et al. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study. Lancet Neurol. 2008;7-7:583-90.

6. Di Fonzo A, Rohe CF, Ferreira J, Chien HF, et al. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet. 2005;365-9457:412-5.

7. Hoffman-Zacharska D, Koziorowski D, Ross OA, et al. Novel A18T and pA29S substitutions in alpha-synuclein may be associated with sporadic Parkinson’s disease. Parkinsonism Relat Disord. 2013;19-11:1057-60.

8. Pirkevi C, Lesage S, Condroyer C, et al. A LRRK2 G2019S mutation carrier from Turkey shares the Japanese haplotype. Neurogenetics. 2009;10-3:271-3.

9. Kessler C, Atasu B, Hanagasi H, et al. Role of LRRK2 and SNCA in autosomal dominant Parkinson’s disease in Turkey. Parkinsonism Relat Disord. 2018;48:34-9.

10. Aslan H, Ozkan S, Tepeli E, et al. Investigation of LRRK2 G2019S Mutation in the Patients with Sporadic Parkinson’s Disease in Turkey. Konuralp Med J. 2014;6-1.

11. Lesage S, Leutenegger A-L, Ibanez P, et al. LRRK2 haplotype analyses in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century. Am J Hum Genet. 2005;77-2:330-2.

12. Lesage S, Dürr A, Tazir M, Lohmann E, et al. LRRK2 G2019S as a cause of Parkinson’s disease in North African Arabs. N Engl J Med. 2006;354-4:422- 3.

13. Gorostidi A, Ruiz-Martinez J, De Munain AL, et al. LRRK2 G2019S and R1441G mutations associated with Parkinson’s disease are common in the Basque Country, but relative prevalence is determined by ethnicity. Neurogenetics. 2009;10-2:157.

14. Mata IF, Hutter CM, González-Fernández MC, et al. Lrrk2 R1441G-related Parkinson’s disease: evidence of a common founding event in the seventh century in Northern Spain. Neurogenetics. 2009;10-4:347-53.

15. Tomiyama H, Li Y, Funayama M, et al. Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson’s disease patients from 18 countries. Mov Disord. 2006;21-8:1102-8.

16. Bialecka M, Hui S, Klodowska-Duda G, et al. Analysis of LRRK2 G2019S and I2020T mutations in Parkinson’s disease. Neurosci Letters. 2005;390- 1:1-3.

17. 1Kumari U, Tan E. LRRK2 in Parkinson’s disease: genetic and clinical studies from patients. FEBS J. 2009;276-22:6455-63