Erken Başlangıçlı Parkinson Hastalığı ve Genetik Sonuçları

Year 2024, Volume: 46 Issue: 2, 236 - 240, 18.03.2024

Hatice Ömercikoğlu Özden Dilek Günal

https://doi.org/10.20515/otd.1358856

Abstract

Genetik ve çevresel faktörler PH gelişmesinde ve ilerlemesinde önemli rol oynar. Bu çalışmada hastanemiz hareket bozuklukları polikliniğinde takipli EBPH’nın genetik test sonuçları ve klinik bulgularının literatür ile karşılaştırılarak değerlendirilmesi amaçlanmıştır. Üniversite hastanesi hareket bozuklukları polikliniğinde erken başlangıçlı Parkinson Hastalığı tanısı ile takip edilen ve genetik tetkikleri yapılmış olan hastaların; demografik özellikleri, klinik bulguları ve genetik test sonuçları retrospektif olarak incelendi. Hareket bozuklukları polikliniğinden takipli, genetik testi yapılmış 43 EBPH’sı çalışmaya alındı. Hastaların 13’ü kadın, 30’u erkekti. Yaş ortalaması 52, hastalık başlangıç yaşı ortalaması 42,8 (25-49) bulundu. Genetik test istenen hastaların %93 ‘ünde PARK-2 ve PINK-1 için 7 ayrı mutasyon saptandı. Hastaların % 7’sinde genetik mutasyon tespit edilmedi. Tremor başlangıç %65, akinetik-rijit başlangıç %35 hastada görüldü. Hiposmi, kabızlık, RUDB gibi prodromal semptomlar genetik testi pozitif saptanan hastaların %57,5’inde görülürken, genetik testi negatif gelen hastaların hiçbirinde mevcut değildi. EBPH’ında tespit edilen benign alel mutasyonların bazılarının EBPH için genetik risk faktörü olabileceği gösterilmiştir. Çalışmamızda benign alel mutasyonların hastalık ile ilişkisini tespit etmek için daha çok sayıda hastanın ve sağlıklı kontrolün katıldığı çok merkezli çalışmalara ihtiyaç olduğuna dikkat çekmek istedik.

Keywords

Parkinson Hastalığı, PARK-2, PINK1

Early Onset Parkinson’s Disease and It’s Genetic Consequences

Abstract

Genetic and environmental factors play an important role in the development and progression of Parkinson’s Disease(PD). In this study, it was aimed to evaluate the genetic test results and clinical findings of early-onset Parkinson's Disease (EOPD) followed up in the movement disorders outpatient clinic of our hospital by comparing them with the literature. Patients who were followed up with the diagnosis of EOPD in the Movement Disorders Outpatient Clinic of Neurology Department, Marmara University Faculty of Medicine and whose genetic tests were performed; demographic characteristics, clinical findings and genetic test results were analyzed retrospectively. Forty-three EOPD patients (13 females, 30 males) who were genetically tested were enrolled in the study. The mean age was 52.3 (range; 31-64 years), and the mean age of disease onset was 42.8 (range; 25-49 years). Seven different mutations for PARK-2 and PINK-1 were detected in 93% of the patients for whom genetic testing was requested. Genetic mutation was not detected in 7% of the patients. While 57.5% of the patients with a positive genetic test had prodromal symptoms such as hyposmia, constipation and Rapid Eye Movement(REM) Sleep Behaviour Disorder (RBD), none of the patients with a negative genetic test had prodromal symptoms. It has been shown that some of the benign allelic mutations detected in EOPD patients may be genetic risk factors for EOPD. In our study, we wanted to draw attention to the need for multicenter studies with larger numbers of patients and healthy controls to determine the relationship between benign allelic mutations and EOPD.

Keywords

Parkinson's Disease, PARK-2, PINK-1

References

• 1. Quinn N, Critchley P, Marsden CD. Young onset Parkinson's disease. Mov Disord. 1987;2(2):73-91.
• 2. Schrag A, Schott JM. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol. 2006;5(4):355-63.
• 3. Golbe LI. Young-onset Parkinson's disease: a clinical review. Neurology. 1991;41(2 ( Pt 1)):168-73.
• 4. Giovannini P, Piccolo I, Genitrini S, Soliveri P, Girotti F, Geminiani G, et al. Early-onset Parkinson's disease. Mov Disord. 1991;6(1):36-42.
• 5. Marras C, Beck JC, Bower JH, Roberts E, Ritz B, Ross GW, et al. Prevalence of Parkinson's disease across North America. NPJ Parkinsons Dis. 2018;4:21.
• 6. Simon DK, Tanner CM, Brundin P. Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clin Geriatr Med. 2020;36(1):1-12.
• 7. Selvaraj S, Piramanayagam S. Impact of gene mutation in the development of Parkinson's disease. Genes Dis. 2019;6(2):120-8.
• 8. Deng H, Le WD, Hunter CB, Ondo WG, Guo Y, Xie WJ, et al. Heterogeneous phenotype in a family with compound heterozygous parkin gene mutations. Arch Neurol. 2006;63(2):273-7.
• 9. Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, et al. Parkin disease: a phenotypic study of a large case series. Brain. 2003;126(Pt 6):1279-92.
• 10. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015;30(12):1591-601.
• 11. Ton ND, Thuan ND, Thuong MTH, Ngoc TTB, Nhung VP, Hoa NTT, et al. Rare and novel variants of PRKN and PINK1 genes in Vietnamese patients with early-onset Parkinson's disease. Mol Genet Genomic Med. 2020;8(10):e1463.
• 12. Zou HQ, Chen B, Ma QL, Li X, Yang JF, Feng XL, et al. [New polymorphism (IVS3-20 T-->C) of the parkin gene associated with the early-onset Parkinson's disease in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004;21(3):219-23.
• 13. Lucking CB, Chesneau V, Lohmann E, Verpillat P, Dulac C, Bonnet AM, et al. Coding polymorphisms in the parkin gene and susceptibility to Parkinson disease. Arch Neurol. 2003;60(9):1253-6.
• 14. Fiala O, Zahorakova D, Pospisilova L, Kucerova J, Matejckova M, Martasek P, et al. Parkin (PARK 2) mutations are rare in Czech patients with early-onset Parkinson's disease. PLoS One. 2014;9(9):e107585.
• 15. Martin-Flores N, Fernandez-Santiago R, Antonelli F, Cerquera C, Moreno V, Marti MJ, et al. MTOR Pathway-Based Discovery of Genetic Susceptibility to L-DOPA-Induced Dyskinesia in Parkinson's Disease Patients. Mol Neurobiol. 2019;56(3):2092-100.
• 16. Bove F, Calabresi P. Plasticity, genetics, and epigenetics in l-dopa-induced dyskinesias. Handb Clin Neurol. 2022;184:167-84.
• 17. Kraemmer J, Smith K, Weintraub D, Guillemot V, Nalls MA, Cormier-Dequaire F, et al. Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2016;87(10):1106-11.
• 18. Morgante F, Fasano A, Ginevrino M, Petrucci S, Ricciardi L, Bove F, et al. Impulsive-compulsive behaviors in parkin-associated Parkinson disease. Neurology. 2016;87(14):1436-41.
• 19. Riboldi GM, Frattini E, Monfrini E, Frucht SJ, Di Fonzo A. A Practical Approach to Early-Onset Parkinsonism. J Parkinsons Dis. 2022;12(1):1-26.
• 20. Marder KS, Tang MX, Mejia-Santana H, Rosado L, Louis ED, Comella CL, et al. Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study. Arch Neurol. 2010;67(6):731-8.
• 21. Aasly JO. Long-Term Outcomes of Genetic Parkinson's Disease. J Mov Disord. 2020;13(2):81-96.