PMID- 12882651
OWN - NLM
STAT- MEDLINE
DCOM- 20031125
LR  - 20181113
IS  - 1471-2377 (Electronic)
IS  - 1471-2377 (Linking)
VI  - 3
DP  - 2003 Jul 26
TI  - A linkage study of candidate loci in familial Parkinson's Disease.
PG  - 6
AB  - BACKGROUND: Parkinson's disease is the second most common neurodegenerative 
      disorder after Alzheimer's disease. Most cases are sporadic, however familial 
      cases do exist. We examined 12 families with familial Parkinson's disease 
      ascertained at the Movement Disorder clinic at the Oregon Health Sciences 
      University for genetic linkage to a number of candidate loci. These loci have 
      been implicated in familial Parkinson's disease or in syndromes with a clinical 
      presentation that overlaps with parkinsonism, as well as potentially in the 
      pathogenesis of the disease. METHODS: The examined loci were PARK3, Parkin, DRD 
      (dopa-responsive dystonia), FET1 (familial essential tremor), BDNF (brain-derived 
      neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), Ret, 
      DAT1 (the dopamine transporter), Nurr1 and Synphilin-1. Linkage to the 
      alpha-synuclein gene and the Frontotemporal dementia with parkinsonism locus on 
      chromosome 17 had previously been excluded in the families included in this 
      study. Using Fastlink, Genehunter and Simwalk both parametric and model-free 
      non-parametric linkage analyses were performed. RESULTS: In the multipoint 
      parametric linkage analysis lod scores were below -2 for all loci except FET1 and 
      Synphilin-1 under an autosomal dominant model with incomplete penetrance. Using 
      non-parametric linkage analysis there was no evidence for linkage, although 
      linkage could not be excluded. A few families showed positive parametric and 
      non-parametric lod scores indicating possible genetic heterogeneity between 
      families, although these scores did not reach any degree of statistical 
      significance. CONCLUSIONS: We conclude that in these families there was no 
      evidence for linkage to any of the loci tested, although we were unable to 
      exclude linkage with both parametric and non-parametric methods.
FAU - Wirdefeldt, Karin
AU  - Wirdefeldt K
AD  - Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 
      karin.wirdefeldt@mep.ki.se
FAU - Burgess, Catherine E
AU  - Burgess CE
FAU - Westerberg, Lisa
AU  - Westerberg L
FAU - Payami, Haydeh
AU  - Payami H
FAU - Schalling, Martin
AU  - Schalling M
LA  - eng
GR  - R01 NS036960/NS/NINDS NIH HHS/United States
GR  - 1 R01 NS36960/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030726
PL  - England
TA  - BMC Neurol
JT  - BMC neurology
JID - 100968555
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (GDNF protein, human)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SLC6A3 protein, human)
RN  - 0 (SNCAIP protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Carrier Proteins/genetics
MH  - Dopamine Plasma Membrane Transport Proteins
MH  - Essential Tremor/genetics
MH  - Female
MH  - Genes, Dominant
MH  - Genetic Linkage/*genetics
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Humans
MH  - Lod Score
MH  - Male
MH  - *Membrane Glycoproteins
MH  - Membrane Transport Proteins/genetics
MH  - Nerve Growth Factors/genetics
MH  - Nerve Tissue Proteins/genetics
MH  - Parkinson Disease/*genetics
MH  - Pedigree
MH  - Penetrance
MH  - Ubiquitin-Protein Ligases/genetics
PMC - PMC184377
EDAT- 2003/07/29 05:00
MHDA- 2003/12/03 05:00
PMCR- 2003/07/26
CRDT- 2003/07/29 05:00
PHST- 2003/04/24 00:00 [received]
PHST- 2003/07/26 00:00 [accepted]
PHST- 2003/07/29 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/07/29 05:00 [entrez]
PHST- 2003/07/26 00:00 [pmc-release]
AID - 1471-2377-3-6 [pii]
AID - 10.1186/1471-2377-3-6 [doi]
PST - ppublish
SO  - BMC Neurol. 2003 Jul 26;3:6. doi: 10.1186/1471-2377-3-6. Epub 2003 Jul 26.