Journal of Neurology

, Volume 258, Issue 12, pp 2260–2267 | Cite as

Phenotype analysis in patients with early onset Parkinson’s disease with and without parkin mutations

  • Hee Jin Kim
  • Han-Joon Kim
  • Jee-Young Lee
  • Ji Young Yun
  • So Yeon Kim
  • Sung Sup Park
  • Beom S. Jeon
Original Communication


The data regarding whether parkin genotype attributes phenotypic variation are conflicting. Since the incidence of parkin mutations is very low in patients with an age at onset (AAO) of >40 years, previous studies have unfairly compared phenotypes of two early onset Parkinson’s disease (EOPD) groups with different AAOs. Thus, we compared the clinical features between patients with and without parkin mutations in EOPD with an AAO of ≤40 years. Of the 124 patients with EOPD with an AAO of ≤40 years who were recruited and screened for parkin mutations, 84 completed assessments for comparison of the phenotype according to parkin genotype. Fourteen of the 84 subjects carried two parkin mutations; 6, a single mutation; and 64, no mutations. Patients with two mutations had significantly younger AAOs, longer duration of PD, and more common family history than patients without parkin mutations. Otherwise, motor and nonmotor symptoms did not differ between them. Subgroup analysis of EOPD with an AAO of ≤35 years revealed similar results. Phenotype of EOPD may depend on early AAOs rather than presence of parkin mutations.


Parkinson’s disease Genetics Movement disorders Neurogenetics 

Supplementary material

415_2011_6110_MOESM1_ESM.doc (151 kb)
Supplementary material 1 (DOC 151 kb)


  1. 1.
    Schrag A, Schott JM (2006) Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol 5:355–363PubMedCrossRefGoogle Scholar
  2. 2.
    Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047PubMedCrossRefGoogle Scholar
  3. 3.
    Hedrich K, Eskelson C, Wilmot B, Marder K, Harris J, Garrels J et al (2004) Distribution, type, and origin of Parkin mutations: review and case studies. Mov Disord 19:1146–1157PubMedCrossRefGoogle Scholar
  4. 4.
    Valente EM, Bentivoglio AR, Dixon PH, Ferraris A, Ialongo T, Frontali M et al (2001) Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK 6, on human chromosome 1p35–p36. Am J Hum Genet 68:895–900PubMedCrossRefGoogle Scholar
  5. 5.
    Van Duijn CM, Dekker MC, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJ et al (2001) PARK 7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet 69:629–634PubMedCrossRefGoogle Scholar
  6. 6.
    Goldwurm S, Di Fonzo A, Simons EJ, Rohé CF, Zini M, Canesi M et al (2005) The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson’s disease and originates from a common ancestor. J Med Genet 42:e65PubMedCrossRefGoogle Scholar
  7. 7.
    Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ et al (2003) Parkin disease: a phenotypic study of a large case series. Brain 126:1279–1292PubMedCrossRefGoogle Scholar
  8. 8.
    Lohmann E, Periquet M, Bonifati V, Wood NW, De Michele G, Bonnet AM et al (2003) How much phenotypic variation can be attributed to parkin genotype? Ann Neurol 54:176–185PubMedCrossRefGoogle Scholar
  9. 9.
    Sironi F, Primignani P, Zini M, Tunesi S, Ruffmann C, Ricca S et al (2008) Parkin analysis in early onset Parkinson’s disease. Parkinsonism Relat Disord 14:326–333PubMedCrossRefGoogle Scholar
  10. 10.
    Macedo MG, Verbaan D, Fang Y, van Rooden SM, Visser M, Anar B et al (2009) Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson’s disease. Mov Disord 24:196–203PubMedCrossRefGoogle Scholar
  11. 11.
    Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T et al (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342:1560–1567PubMedCrossRefGoogle Scholar
  12. 12.
    Yamamura Y, Hattori N, Matsumine H, Kuzuhara S, Mizuno Y (2000) Autosomal recessive early-onset parkinsonism with diurnal fluctuation: clinicopathologic characteristics and molecular genetic identification. Brain Dev 22(suppl 1):S87–S91PubMedCrossRefGoogle Scholar
  13. 13.
    Thobois S, Ribeiro MJ, Lohmann E, Dürr A, Pollak P, Rascol O (2003) French Parkinson’s Disease Genetics Study Group. Young-onset Parkinson disease with and without parkin gene mutations: a fluorodopa F 18 positron emission tomography study. Arch Neurol 60:713–718PubMedCrossRefGoogle Scholar
  14. 14.
    Clark LN, Afridi S, Karlins E, Wang Y, Mejia-Santana H, Harris J et al (2006) Case-control study of the parkin gene in early-onset Parkinson disease. Arch Neurol 63:548–552PubMedCrossRefGoogle Scholar
  15. 15.
    Lohmann E, Thobois S, Lesage S, Broussolle E, du Montcel ST, Ribeiro MJ et al (2009) A multidisciplinary study of patients with early-onset PD with and without parkin mutations. Neurology 72:110–116PubMedCrossRefGoogle Scholar
  16. 16.
    Periquet M, Latouche M, Lohmann E, Rawal N, De Michele G, Ricard S et al (2003) Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain 126:1271–1278PubMedCrossRefGoogle Scholar
  17. 17.
    Chung EJ, Ki CS, Lee WY, Kim IS, Kim JY (2006) Clinical features and gene analysis in Korean patients with early-onset Parkinson disease. Arch Neurol 63:1170–1174PubMedCrossRefGoogle Scholar
  18. 18.
    Choi JM, Woo MS, Ma HI, Kang SY, Sung YH, Yong SW et al (2008) Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease. Neurogenetics 9:263–269PubMedCrossRefGoogle Scholar
  19. 19.
    Marder KS, Tang MX, Mejia-Santana H, Rosado L, Louis ED, Comella CL et al (2010) Predictors of parkin mutations in early-onset Parkinson disease: the consortium on risk for early-onset Parkinson disease study. Arch Neurol 67:731–738PubMedCrossRefGoogle Scholar
  20. 20.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184PubMedCrossRefGoogle Scholar
  21. 21.
    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedGoogle Scholar
  22. 22.
    Kim HJ, Paek SH, Kim JY, Lee JY, Lim YH, Kim MR et al (2008) Chronic subthalamic deep brain stimulation improves pain in Parkinson disease. J Neurol 255:1889–1894PubMedCrossRefGoogle Scholar
  23. 23.
    Chaudhuri KR, Martinez-Martin P, Schapira AH, Stocchi F, Sethi K, Odin P et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 21:916–923PubMedCrossRefGoogle Scholar
  24. 24.
    Kaufer DI, Cummings JL, Ketchel P, Smith V, MacMillan A, Shelley T et al (2000) Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci 12:233–239PubMedCrossRefGoogle Scholar
  25. 25.
    Beck AT, Ward CH, Mendelson M (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571PubMedGoogle Scholar
  26. 26.
    Lee JY, Kim JM, Kim JW, Cho J, Lee WY, Kim HJ et al (2010) Association between the dose of dopaminergic medication and the behavioral disturbances in Parkinson disease. Parkinsonism Relat Disord 16:202–207PubMedCrossRefGoogle Scholar
  27. 27.
    Kim SY, Seong MW, Jeon BS, Kim SY, Ko HS, Kim JY, et al (2011) Phase analysis identifies compound heterozygous deletions of the PARK2 gene in patients with early-onset Parkinson disease. Clin Genet (Epub ahead of print) doi:10.1111/j.1399-0004.2011.01693.x
  28. 28.
    Ahn TB, Kim SY, Kim JY, Park SS, Lee DS, Min HJ et al (2008) a-Synuclein gene duplication is present in sporadic Parkinson disease. Neurology 70:43–49PubMedCrossRefGoogle Scholar
  29. 29.
    Cho JW, Kim SY, Park SS, Jeon BS (2009) The G2019S LRRK2 mutation is rare in Korean patients with Parkinson’s disease and multiple system atrophy. J Clin Neurol 5:29–32PubMedCrossRefGoogle Scholar
  30. 30.
    Kim JM, Hong S, Kim GP, Choi YJ, Kim YK, Park SS et al (2007) Importance of low range CAG expansion and CAA interruption in SCA2 Parkinsonism. Arch Neurol 64:1510–1518PubMedCrossRefGoogle Scholar
  31. 31.
    Kim JY, Kim SY, Kim JM, Kim YK, Yoon KY, Kim JY et al (2009) Spinocerebellar ataxia type 17 mutation as a causative and susceptibility gene in parkinsonism. Neurology 72:1385–1389PubMedCrossRefGoogle Scholar
  32. 32.
    Wu RM, Bounds R, Lincoln S, Hulihan M, Lin CH, Hwu WL et al (2005) Parkin mutations and early-onset parkinsonism in a Taiwanese cohort. Arch Neurol 62:82–87PubMedCrossRefGoogle Scholar
  33. 33.
    Wang T, Liang ZH, Sun SG, Cao XB, Peng H, Liu HJ et al (2004) Systematic examination of DNA variants in the parkin gene in patients with Parkinson’s disease. Chin Med J 117:1567–1569PubMedGoogle Scholar
  34. 34.
    Periquet M, Latouche M, Lohmann E, Rawal N, De Michele G, Ricard S et al (2003) French Parkinson’s disease genetics study group; European Consortium on Genetic Susceptibility in Parkinson’s disease Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain 126:1271–1278PubMedCrossRefGoogle Scholar
  35. 35.
    Yamamura Y, Sobue I, Ando K, Iida M, Yanagi T (1973) Paralysis agitans of early onset with marked diurnal fluctuation of symptoms. Neurology 23:239–244PubMedGoogle Scholar
  36. 36.
    Haehner A, Boesveldt S, Berendse HW, Mackay-Sim A, Fleischmann J, Silburn PA et al (2009) Prevalence of smell loss in Parkinson’s disease—a multicenter study. Parkinsonism Relat Disord 15:490–494PubMedCrossRefGoogle Scholar
  37. 37.
    Khan NL, Katzenschlager R, Watt H, Bhatia KP, Wood NW, Quinn N et al (2004) Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Neurology 62:1224–1226PubMedGoogle Scholar
  38. 38.
    Verbaan D, Boesveldt S, van Rooden SM, Visser M, Marinus J, Macedo MG et al (2008) Is olfactory impairment in Parkinson disease related to phenotypic or genotypic characteristics? Neurology 71:1877–1882PubMedCrossRefGoogle Scholar
  39. 39.
    Kagi G, Klein C, Wood NW, Schneider SA, Pramstaller PP, Tadic V et al (2010) Nonmotor symptoms in Parkin gene-related parkinsonism. Mov Disord 25:1279–1284PubMedCrossRefGoogle Scholar
  40. 40.
    Kasten M, Kertelge L, Brüggemann N, van der Vegt J, Schmidt A, Tadic V et al (2010) Nonmotor symptoms in genetic Parkinson disease. Arch Neurol 67:670–676PubMedCrossRefGoogle Scholar
  41. 41.
    Alcalay RN, Siderowf A, Ottman R, Caccappolo E, Mejia-Santana H, Tang MX et al (2011) Olfaction in Parkin heterozygotes and compound heterozygotes: the CORE-PD study. Neurology 76:319–326PubMedCrossRefGoogle Scholar
  42. 42.
    Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP et al (2009) PRIAMO study group The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 24:1641–1649PubMedCrossRefGoogle Scholar
  43. 43.
    Weintraub D, Koester J, Potenza MN, Siderowf AD, Stacy M, Voon V et al (2010) Impulse control disorders in Parkinson disease: a cross-sectional study of 3,090 patients. Arch Neurol 67:589–595PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hee Jin Kim
    • 1
    • 2
  • Han-Joon Kim
    • 2
    • 3
  • Jee-Young Lee
    • 2
    • 4
  • Ji Young Yun
    • 2
    • 5
  • So Yeon Kim
    • 6
  • Sung Sup Park
    • 6
  • Beom S. Jeon
    • 2
    • 3
    • 7
    • 8
  1. 1.Department of NeurologyKonkuk University HospitalSeoulKorea
  2. 2.Parkinson Disease Study Group, Clinical Research InstituteSeoul National University HospitalSeoulKorea
  3. 3.Department of NeurologySeoul National University HospitalSeoulKorea
  4. 4.Department of NeurologySeoul National University Boramae HospitalSeoulKorea
  5. 5.Department of NeurologySeoul National University HospitalSeoulKorea
  6. 6.Department of Laboratory MedicineSeoul National University HospitalSeoulKorea
  7. 7.Neuroscience Research Institute, College of MedicineSeoul National UniversitySeoulKorea
  8. 8.Office of Health Care Policy, College of MedicineSeoul National University HospitalSeoulKorea

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