Biomedical subjects

Haydeh Payami

Publications and source records attributed to Haydeh Payami.

24 records · Page 2Linked to original sources

PubMed2003

A linkage study of candidate loci in familial Parkinson's Disease.

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.

Brain-Derived Neurotrophic Factor↗

PubMed2003

SCA2 may present as levodopa-responsive parkinsonism.

Some kindreds with familial parkinsonism exhibit genetic anticipation, suggesting possible involvement of trinucleotide repeat expansion. Recent reports have shown trinucleotide repeat expansions in the spinocerebellar ataxia 2 (SCA2) gene in patients with levodopa-responsive parkinsonism. We tested 136 unrelated patients with familial parkinsonism for SCA2 mutations. Two probands had borderline mutations; the rest were normal. ( or=36 is pathogenic). The expanded allele segregated with neurological signs in one kindred. The absence of borderline mutations in the normal population, and the co-segregation of the expanded allele with neurological signs in one kindred suggest that SCA2 mutations may be responsible for a subset of familial parkinsonism.

Adult↗

PubMed2002

Age at onset of Parkinson disease and apolipoprotein E genotypes.

Several lines of evidence suggest that the variable age at onset of Parkinson disease (PD) is likely influenced by genes. The apolipoprotein E (APOE) gene is associated with onset of Alzheimer disease, and possibly other neurodegenerative disorders. APOE has been investigated in relation to onset of PD, but results have been inconsistent. The aim of the present study was to determine if APOE genotypes are associated with onset age of PD, using a patient population large enough to assure sufficient power. We studied 521 unrelated Caucasian patients with idiopathic PD from movement disorder clinics in Oregon and Washington. Genotyping and statistical analyses were carried out using standard methods. Age at onset of PD was significantly earlier in patients with the varepsilon3varepsilon4/varepsilon4varepsilon4 genotype than in patients with the varepsilon3varepsilon3 genotype (56.1 +/- 10.9 vs. 59.6 +/- 11.0, P = 0.003). The significantly earlier onset of PD was not influenced by the possible effects of recruitment site, family history and gender. The effect of the varepsilon2varepsilon3 genotype on onset of PD differed between the two recruitment sites. There was a trend for earlier onset of PD in varepsilon2varepsilon3 patients than in varepsilon3varepsilon3 patients only in the Oregon sample. In conclusion, APOE is associated with age at onset of PD.

Age of Onset↗

PubMed2002

Independent predictors of cognitive decline in healthy elderly persons.

BACKGROUND: Several studies have shown that individually memory, hippocampal volume, and motor measures presage the onset of dementia. It is unclear if these independently contribute to the prediction of mild cognitive impairment. OBJECTIVE: To determine the ability of memory, hippocampal volume, and a gait speed to independently predict cognitive decline in healthy elderly persons. DESIGN: A prospective, longitudinal, observational cohort study with a mean follow-up of 6 years. PARTICIPANTS: One hundred eight optimally healthy elderly cognitively intact subjects. MAIN OUTCOME MEASURES: Any cognitive impairment noted on the Clinical Dementia Rating Scale (score = 0.5) or persistent or progressive cognitive impairment. Cox modeling determined if time to onset of cognitive impairment was associated with baseline logical memory II test score (a measure of delayed recall), hippocampal volume (magnetic resonance imaging), or gait speed (time to walk 30 ft [9 m]) independent of age, sex, depression, or the allele producing the epsilon4 type of apolipoprotein E (APOE epsilon4). RESULTS: Questionable dementia occurred in 48 participants in a mean (SD) of 3.7 (2.4) years. This progressed to persistent cognitive impairment in 38 of these participants in a mean (SD) of 4.4 (2.4) years. Logical memory II test performance and hippocampal volume each predicted onset of questionable dementia, independent of age and sex. Time to walk 30 ft additionally contributed independently to the prediction of time to onset of persistent cognitive impairment. Possessing the APOE epsilon4 allele and depression did not enter either model significantly. CONCLUSIONS: Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention.

Aged↗

PubMed2002

Familial aggregation of Parkinson disease: a comparative study of early-onset and late-onset disease.

CONTEXT: It is unclear whether late-onset Parkinson disease (PD), which is the most typical and most common form of the disease, has a familial component. Evidence for familial aggregation is key to whether research should focus on gene discovery or search for environmental factors. OBJECTIVE: To investigate familial aggregation of early-onset and late-onset PD separately. METHODS: Using survival methods, age-specific risk of PD was calculated and compared for 525 parents and siblings of 117 patients with early-onset PD, 1642 parents and siblings of 343 patients with late-onset PD, and 522 parents and siblings of 114 controls. The index patients were ascertained from a movement disorder clinic. Spouses and friends served as controls. RESULTS: Compared with the relatives of controls, age-specific risk of PD was increased 7.76-fold in the relatives of patients with early-onset disease (P<.001) and 2.95-fold in the relatives of those with late-onset disease (P =.02). CONCLUSIONS: Late-onset PD has a significant familial component. The magnitude of recurrence risk to relatives suggests a genetic etiology, without ruling out the possibility of a coexisting environmental component.

Adult↗

PubMed2002

Accurate determination of ataxin-2 polyglutamine expansion in patients with intermediate-range repeats.

Spinocerebellar ataxia, type 2 (SCA2), results from an expansion of a stretch of polyglutamine repeats within the coding sequence of the ataxin-2 gene (ATX2), localized to chromosome 12q23-24. Recent studies have widened the clinical phenotype, notably for individuals with repeats of intermediate size, from 32 to 35 glutamine residues. This narrow range necessitates precise determination of repeat size. Diagnostic laboratories most often perform direct genotyping of ATX2 from polymerase chain-amplified patient DNA with subsequent sizing utilizing slab gel polyacrylamide gel electrophoresis (PAGE) or capillary electrophoresis. Using cloning and sequencing methods, we have constructed a ladder of ATX2 alleles of known size and sequence composition. This freely available size ladder will facilitate future quantification of expansions of the ATX2 locus.

Ataxins↗