title: Dopaminergic function in a family with the PARK6 form of autosomal recessive Parkinson's syndrome.
abstract: A G309D mutation in the PINK1 gene in a consanguineous Spanish kindred with seven siblings, three of whom are clinically affected, has recently been shown to be a cause of the PARK6 form of autosomal-recessive Parkinson's syndrome. In this family, we studied pre- and postsynaptic dopaminergic function using 123I-FP-CIT- and 123I-iodobenzamide-SPECT to determine binding to the presynaptic dopamine transporter (DAT) and postsynaptic D2 receptors respectively. All three PARK6 patients showed reduced striatal DAT binding with posterior preponderance similar to sporadic idiopathic PD, but only one patient showed significant striatal asymmetry. In two of the siblings, DAT binding was markedly increased. IBZM-SPECT was normal in both patients and sibs. Our findings indicate that 123I-FP-CIT-SPECT shows similar DAT binding in PARK6 patients compared to idiopathic Parkinson's disease. The increased DAT binding in heterozygous PARK6 carriers may be a new very early preclinical finding, but its significance is still unclear.
authors.affiliation: Department of Neurology, J.W. Goethe University, Frankfurt/Main, Germany.
authors.forename: K R
authors.initials: KR
authors.lastname: Kessler
authors.forename: N
authors.initials: N
authors.lastname: Hamscho
authors.forename: B
authors.initials: B
authors.lastname: Morales
authors.forename: C
authors.initials: C
authors.lastname: Menzel
authors.forename: F
authors.initials: F
authors.lastname: Barrero
authors.forename: F
authors.initials: F
authors.lastname: Vives
authors.forename: S
authors.initials: S
authors.lastname: Gispert
authors.forename: G
authors.initials: G
authors.lastname: Auburger
mesh_terms: D000328:Adult; D001549:Benzamides; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D011759:Pyrrolidines; D035781:Siblings; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes; D000099202:PTEN-Induced Putative Kinase
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D004298:Dopamine; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D011494:Protein Kinases; D011759:Pyrrolidines; D014326:Tropanes; D000099202:PTEN-Induced Putative Kinase; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide