Clinical and genetic evaluation of 8 Polish families with levodopa-responsive parkinsonism

J Neural Transm (Vienna). 2005 Nov;112(11):1487-502. doi: 10.1007/s00702-005-0290-8. Epub 2005 Mar 23.

Abstract

We studied 8 large Polish families with parkinsonism, 6 of which were newly identified. Thirty-six family members had well-documented levodopa-responsive parkinsonism. The phenotype of affected individuals was indistinguishable from that of persons with idiopathic Parkinson disease (PD). The pattern of inheritance in 5 families was consistent with autosomal dominant transmission; in 3 families the mode of inheritance was uncertain. Single photon emission computed tomography (SPECT) studies with the dopamine transporter radioligand [(123)I]FP-CIT were performed in 1 family. The SPECT study showed striatal presynaptic dopaminergic degeneration consistent with sporadic PD in 1 affected family member and no signs of nigrostriatal dopaminergic dysfunction in 5 at-risk individuals. Sequence analysis in all 8 families excluded known genes associated with familial parkinsonism. Genome-wide 2-point linkage studies in the largest 2 families did not identify significant linkage (z > 3.0), although positive scores were obtained for 5q23 (D5S1462 and D5S2501), a locus previously implicated in disease susceptibility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / pharmacology
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / physiopathology*
  • Chromosome Mapping
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiopathology
  • DNA Mutational Analysis
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Inheritance Patterns / genetics
  • Levodopa / pharmacology*
  • Male
  • Middle Aged
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Parkinsonian Disorders / diagnostic imaging
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / genetics*
  • Pedigree
  • Poland
  • Substantia Nigra / diagnostic imaging
  • Substantia Nigra / metabolism
  • Substantia Nigra / physiopathology
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Antiparkinson Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Levodopa