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  • Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families

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Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinson's disease families
  1. W C Nichols1,
  2. N Pankratz2,
  3. S K Uniacke1,
  4. M W Pauciulo1,
  5. C Halter2,
  6. A Rudolph3,
  7. P M Conneally2,
  8. T Foroud2,
  9. The Parkinson Study Group
  1. 1Division of Human Genetics, Children's Hospital Medical Center, Cincinnati, OH, USA
  2. 2Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis, IN, USA
  3. 3Department of Neurology, University of Rochester, Rochester, NY, USA
  1. Correspondence to:
 Dr W C Nichols, Division of Human Genetics, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA;
 bill.nichols{at}chmcc.org

https://doi.org/10.1136/jmg.39.7.489

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    Parkinson's disease (PD) is one of the most common neurological disorders in humans with an overall prevalence of 1:1000 with the incidence increasing to as high as 3.4% among people aged 75 years.1,2 The clinical phenotype includes resting tremor, muscular rigidity, bradykinesia, and postural instability. The signs and symptoms of the disease are the consequence of a striatal deficiency of dopamine resulting from neuronal death in the substantia nigra. It is characterised by the presence of the Lewy body, an intracytoplasmic inclusion body found in many brain regions which is not entirely specific to, but is a highly sensitive marker for, Parkinson's disease.

    The pathogenesis of idiopathic Parkinson's disease is unknown. For the overwhelming majority of PD patients, the disease has previously been thought to occur sporadically. However, there is increasing evidence of a genetic contribution to the disorder.1,3 Recently, two studies have investigated familial aggregation of PD using large, population based, case-control studies. Elbaz et al4 reported an odds ratio of 3.2 for the presence of PD in first degree relatives (parents and sibs) of 175 cases as compared to 481 controls. Analyses stratified by age showed this aggregation to be stronger for younger PD patients. Familial aggregation of PD in Iceland was studied using a cohort of 772 cases, with 560 having onset of disease at >50 years of age.5 In this study, the odds ratio for PD was 6.7 for sibs and 3.2 for offspring of affected subjects. These studies are consistent with others reporting the risk to be anywhere from two to 14 times higher for first degree relatives as compared to the risk in members of unaffected families.6–9

    Genetic linkage analyses in families with either autosomal dominant forms of PD or with an autosomal recessive, juvenile form …

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