title: Clinical and genetic evaluation of 8 Polish families with levodopa-responsive parkinsonism.
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.
authors.affiliation: Department of Neurology, Collegium Medicum, Jagiellonian University, Kraków, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Krygowska-Wajs
authors.forename: J M
authors.initials: JM
authors.lastname: Kachergus
authors.forename: M M
authors.initials: MM
authors.lastname: Hulihan
authors.forename: M J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: J A
authors.initials: JA
authors.lastname: Searcy
authors.forename: J
authors.initials: J
authors.lastname: Booij
authors.forename: H W
authors.initials: HW
authors.lastname: Berendse
authors.forename: E Ch
authors.initials: ECh
authors.lastname: Wolters
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D002874:Chromosome Mapping; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D010375:Pedigree; D011044:Poland; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D007980:Levodopa