A large kindred with autosomal dominant Parkinson's disease

Authors

  • Lawrence I. Golbe MD,

    Corresponding author
    1. Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ
    • Department of Neurology, UMDNJ-Robert Wood Johnson Medical School, CN-19, New Brunswick, NJ 08903
    Search for more papers by this author
  • Giuseppe Di Iorio MD,

    1. Istituto di Scienze Neurologiche, Università degli studi do Napoli, Naples, Italy
    Search for more papers by this author
  • Vincenzo Bonavita MD,

    1. Istituto di Scienze Neurologiche, Università degli studi do Napoli, Naples, Italy
    Search for more papers by this author
  • Douglas C. Miller MD PhD,

    1. Department of Pathology (Neuropathology), New York University-Bellevue Medical Center, New York, NY
    Search for more papers by this author
  • Roger C. Duvoisin MD

    1. Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ
    Search for more papers by this author

Abstract

We report two large kindreds with Parkinson's disease (PD) apparently inherited in autosomal dominant fashion. Forty-one persons in four generations have been affected; we have examined 7 of them. The two kindreds originated in a single small town in southern Italy and therefore are probably related. The illness was typical for PD except for early onset at a mean age of 46.5 years and a rapid course that averaged 9.7 years from onset to death. Clinical appearance and response to levodopa were typical for PD. Only one instance of difinite nonpenetrance is known. Autopsy of 2 patients in one kindred showed the pathological changes typical of PD with Lewy bodies. Disease duration among affected persons who spent most of their lives in Italy was longer than for their affected US relatives, suggesting that exogenous agents may influence the course of this genetic illness. We conclude that what is probably a single gene without an additional environmental insult can cause the pathological changes typical of PD. Our findings therefore enhance the likelihood of significant genetic component in the cause of sporadic PD. By identifying a toxic gene product, future molecular genetic studies in our kindred(s) may provide insight into the pathogenesis of sporadic PD.

Ancillary