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The Genetics of Parkinson’s Disease

Yıl 2024, Cilt: 34 Sayı: 1, 136 - 143, 29.02.2024
https://doi.org/10.54005/geneltip.1337447

Öz

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Approximately 15% of PD patients have a family history of the disease in one or more first-degree relatives, and 5-10% of PD cases exhibit a classical Mendelian inheritance pattern. In 1997, the heritable transmission of PD was first documented. Recent studies have found 90 independent genome-wide signals at 78 loci that may be associated with PD. The identification of genes linked to PD and their functions has uncovered novel biological pathways and treatment options that play a role in the development of PD. In this article, it is aimed to review up-to-date information on the genetics of PD.

Kaynakça

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  • Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of α-synuclein causes parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164–73.
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Parkinson Hastalığı Genetiği

Yıl 2024, Cilt: 34 Sayı: 1, 136 - 143, 29.02.2024
https://doi.org/10.54005/geneltip.1337447

Öz

Parkinson hastalığı (PH), dünya çapında en yaygın nörodejeneratif hastalıklardan biridir. PH hastalarının yaklaşık %15'inde bir veya daha fazla birinci derece akrabada hastalık öyküsü vardır ve PH vakalarının %5-10'u klasik Mendel kalıtım modeli sergiler. 1997'de, PH'nın kalıtsal geçişi ilk kez belgelenmiştir. Son yapılan araştırmalarda, PD ile ilişkili olabilecek 78 lokusta 90 bağımsız genom çapında sinyal bulunmuştur. PH ile bağlantılı genlerin ve bunların işlevlerinin tanımlanması, PH gelişiminde rol oynayan yeni biyolojik yolları ve tedavi seçeneklerini ortaya çıkmasını sağlamıştır. Bu yazıda Parkinson hastalığının genetiği ile ilgili güncel bilgilerin gözden geçirilmesi amaçlanmıştır.

Kaynakça

  • Kalia L V, Lang AE. Parkinson’s disease. The Lancet. 2015 Aug;386(9996):896–912.
  • Rocca WA. The burden of Parkinson’s disease: a worldwide perspective. Lancet Neurol. 2018 Nov;17(11):928–9.
  • Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020 Jan 27;27(1):27–42.
  • Yalçın Çakmaklı G EB. Parkinson Hastalığında Patogenez. Türkiye Klinikleri. 2021;5–10.
  • Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr 1;79(4):368–76.
  • Lesage S, Brice A. Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Mol Genet. 2009 Apr 15;18(R1):R48–59.
  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the α-Synuclein Gene Identified in Families with Parkinson’s Disease. Science (1979). 1997 Jun 27;276(5321):2045–7.
  • Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019 Dec;18(12):1091–102.
  • Marras C, Lang A, van de Warrenburg BP, Sue CM, Tabrizi SJ, Bertram L, et al. Nomenclature of genetic movement disorders: Recommendations of the international Parkinson and movement disorder society task force. Movement Disorders. 2016 Apr;31(4):436–57.
  • Cook Shukla L SJFJ et al. Parkinson Disease Overview.2004 May 25 [Updated 2019 Jul 25]. In: In: Adam MP MGPR et al. , editors. G [Internet]., editor. GeneReviews® [Internet] Seattle (WA): University of Washington, Seattle; 1993-2023 [Internet]. [cited 2023 Jul 14]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1223/
  • Bonini NM, Giasson BI. Snaring the Function of α-Synuclein. Cell. 2005 Nov;123(3):359–61.
  • Lesage S, Anheim M, Letournel F, Bousset L, Honoré A, Rozas N, et al. G51D α-synuclein mutation causes a novel Parkinsonian-pyramidal syndrome. Ann Neurol. 2013 Apr;73(4):459–71.
  • Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I, et al. The new mutation, E46K, of α-synuclein causes parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164–73.
  • Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S, et al. AlaSOPro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat Genet. 1998 Feb;18(2):106–8.
  • Kiely AP, Asi YT, Kara E, Limousin P, Ling H, Lewis P, et al. α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy? Acta Neuropathol. 2013 May 12;125(5):753–69.
  • Ross OA, Braithwaite AT, Skipper LM, Kachergus J, Hulihan MM, Middleton FA, et al. Genomic investigation of α-synuclein multiplication and parkinsonism. Ann Neurol. 2008 Jun;63(6):743–50.
  • Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. α-Synuclein Locus Triplication Causes Parkinson’s Disease. Science (1979). 2003 Oct 31;302(5646):841–841.
  • Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F. A new locus for Parkinson’s disease (PARK8) maps to chromosome 12p11.2-q13.1. Ann Neurol. 2002 Mar;51(3):296–301.
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  • Camargos ST, Dornas LO, Momeni P, Lees A, Hardy J, Singleton A, et al. Familial Parkinsonism and early onset Parkinson’s disease in a Brazilian movement disorders clinic: Phenotypic characterization and frequency of SNCA , PRKN , PINK1 , and LRRK2 mutations. Movement Disorders. 2009 Apr 15;24(5):662–6.
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  • Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism. Science (1979). 2003 Jan 10;299(5604):256–9.
  • Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism. Science (1979). 2003 Jan 10;299(5604):256–9.
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  • Pankratz N, Pauciulo MW, Elsaesser VE, Marek DK, Halter CA, Wojcieszek J, et al. Mutations in DJ-1 are rare in familial Parkinson disease. Neurosci Lett. 2006 Nov;408(3):209–13.
  • Annesi G, Savettieri G, Pugliese P, D’Amelio M, Tarantino P, Ragonese P, et al. DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex. Ann Neurol. 2005 Nov;58(5):803–7.
  • Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW. The role of pathogenic DJ-1 mutations in Parkinson’s disease. Ann Neurol. 2003 Sep;54(3):283–6.
  • Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, et al. Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism. Science (1979). 2003 Jan 10;299(5604):256–9.
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Toplam 98 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Tıbbi Genetik (Kanser Genetiği hariç), Klinik Tıp Bilimleri (Diğer)
Bölüm Review
Yazarlar

Zeliha Yücel 0000-0002-2303-9704

Levent Şimşek 0000-0001-7729-3970

Emine Berrin Yüksel 0000-0001-7107-1939

Erken Görünüm Tarihi 26 Şubat 2024
Yayımlanma Tarihi 29 Şubat 2024
Gönderilme Tarihi 3 Ağustos 2023
Yayımlandığı Sayı Yıl 2024 Cilt: 34 Sayı: 1

Kaynak Göster

Vancouver Yücel Z, Şimşek L, Yüksel EB. The Genetics of Parkinson’s Disease. Genel Tıp Derg. 2024;34(1):136-43.