Dataset Information

Characterization of DCTN1 genetic variability in neurodegeneration.

ABSTRACT:

Objective

Recently, mutations in DCTN1 were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration.

Methods

In this study we sequenced all DCTN1 exons and exon-intron boundaries in 286 samples diagnosed with Parkinson disease (PD), frontotemporal lobar degeneration (FTLD), or ALS.

Results

This analysis revealed 36 novel variants (9 missense, 5 silent, and 22 noncoding). Segregation analysis in families and association studies in PD, FTLD, and ALS case-control series did not identify any variants segregating with disease or associated with increased disease risk.

Conclusions

This study suggests that pathogenic mutations in DCTN1 are rare and do not play a common role in the development of Parkinson disease, frontotemporal lobar degeneration, or amyotrophic lateral sclerosis.

SUBMITTER: Vilarino-Guell C

PROVIDER: S-EPMC2692178 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Characterization of DCTN1 genetic variability in neurodegeneration.

Vilariño-Güell C C Wider C C Soto-Ortolaza A I AI Cobb S A SA Kachergus J M JM Keeling B H BH Dachsel J C JC Hulihan M M MM Dickson D W DW Wszolek Z K ZK Uitti R J RJ Graff-Radford N R NR Boeve B F BF Josephs K A KA Miller B B Boylan K B KB Gwinn K K Adler C H CH Aasly J O JO Hentati F F Destée A A Krygowska-Wajs A A Chartier-Harlin M-C MC Ross O A OA Rademakers R R Farrer M J MJ

Neurology 20090601 23

<h4>Objective</h4>Recently, mutations in DCTN1 were found to cause Perry syndrome, a parkinsonian disorder with TDP-43-positive pathology. Previously, mutations in DCTN1 were identified in a family with lower motor neuron disease, in amyotrophic lateral sclerosis (ALS), and in a family with ALS/frontotemporal dementia (FTD), suggesting a central role for DCTN1 in neurodegeneration.<h4>Methods</h4>In this study we sequenced all DCTN1 exons and exon-intron boundaries in 286 samples diagnosed with ...[more]

PMID: 19506225

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Project description:Objective: Increased variability in cognition with age has been argued as an indication of pathological processes. Focusing on early detection of neurodegenerative disorders, we investigated variability in cognition in healthy middle-aged adults. In order to understand possible determinants of this variability, we also investigated associations with cognitive reserve, neuroimaging markers, subjective memory complaints, depressive symptomatology, and gender. Method: Thirty-one 50 ± 2 years old individuals were investigated as target group and deviation was studied in comparison to a reference younger group of 30 individuals 40 ± 2 years old. Comprehensive neuropsychological and structural imaging protocols were collected. Brain regional volumes and cortical thickness were calculated with FreeSurfer, white matter hyperintensities with CASCADE, and mean diffusivity with FSL. Results: Across-individuals variability showed greater dispersion in lexical access, processing speed, executive functions, and memory. Variability in global cognition correlated with, reduced cortical thickness in the right parietal-temporal-occipital association cortex, and increased mean diffusivity in the cingulum bundle and right inferior fronto-occipital fasciculus. A trend was also observed for the correlation between global cognition and hippocampal volume and female gender. All these associations were influenced by cognitive reserve. No correlations were found with subjective memory complaints, white matter hyperintensities and depressive symptomatology. Across-domains and across-tasks variability was greater in several executive components and cognitive processing speed. Conclusion: Variability in cognition during middle-age is associated with neurodegeneration in the parietal-temporal-occipital association cortex and white matter tracts connecting this to the prefrontal dorsolateral cortex and the hippocampus. Moreover, this effect is influenced by cognitive reserve. Studying variability offers valuable information showing that differences do not occur in the same magnitude and direction across individuals, cognitive domains and tasks. These findings may have important implications for early detection of subtle cognitive impairment and clinical interpretation of deviation from normality.

Dataset Information

Characterization of DCTN1 genetic variability in neurodegeneration.

Objective

Methods

Results

Conclusions

Publications

Characterization of DCTN1 genetic variability in neurodegeneration.

Similar Datasets

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