Enter Your Search:
Results 1-3 (3)
Go to page number:
Clear All Filters
BMC Neurology (1)
European Journal of Human Genetics (1)
PLoS Currents (1)
Nielsen, Troels Tolstrup
Nielsen, Jørgen E (2)
Aidt, Frederik Heurlin (1)
Bech, Sara (1)
Christiansen, Michael (1)
Duno, Morten (1)
Ehrenfels, Susanne (1)
Ek, Jakob (1)
Friberg, Lars (1)
Hagen, Christian Munch (1)
Hasholt, Lis (1)
Hjermind, Lena E (1)
Kanters, Jørgen (1)
Løkkegaard, Annemette (1)
Mardosiene, Skirmante (1)
Nielsen, Jens Kellberg (1)
Nielsen, Signe Marie Borch (1)
Nørremølle, Anne (1)
Pesta, Dominik (1)
Skovby, Flemming (1)
Stokholm, Jette (1)
Vinther-Jensen, Tua (1)
Year of Publication
Did you mean:
author:("Nielsen, Troels thylstrup")
Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2
Hjermind, Lena E
Nielsen, Jørgen E
European Journal of Human Genetics
The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which – like CAG codons – code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.
spinocerebellar ataxia type 2; ATXN2; CAG repeat instability
Dysfunctional mitochondrial respiration in the striatum of the Huntington’s disease transgenic R6/2 mouse model
Aidt, Frederik Heurlin
Nielsen, Signe Marie Borch
Hagen, Christian Munch
Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system (ETS). In different models of HD, evidence of enzyme defects have been reported in complex II and complex IV using enzyme assays. However, such assays are highly variable and results have been inconsistent. We investigated the integrated ETS function ex vivo using a sensitive high-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in complex II and complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays.
Severe and rapidly progressing cognitive phenotype in a SCA17-family with only marginally expanded CAG/CAA repeats in the TATA-box binding protein gene: A case report
Nielsen, Jens Kellberg
Nielsen, Jørgen E
The autosomal dominant spinocerebellar ataxias (SCAs) confine a group of rare and heterogeneous disorders, which present with progressive ataxia and numerous other features e.g. peripheral neuropathy, macular degeneration and cognitive impairment, and a subset of these disorders is caused by CAG-repeat expansions in their respective genes. The diagnosing of the SCAs is often difficult due to the phenotypic overlap among several of the subtypes and with other neurodegenerative disorders e.g. Huntington’s disease.
We report a family in which the proband had rapidly progressing cognitive decline and only subtle cerebellar symptoms from age 42. Sequencing of the TATA-box binding protein gene revealed a modest elongation of the CAG/CAA-repeat of only two repeats above the non-pathogenic threshold of 41, confirming a diagnosis of SCA17. Normally, repeats within this range show reduced penetrance and result in a milder disease course with slower progression and later age of onset. Thus, this case presented with an unusual phenotype.
The current case highlights the diagnostic challenge of neurodegenerative disorders and the need for a thorough clinical and paraclinical examination of patients presenting with rapid cognitive decline to make a precise diagnosis on which further genetic counseling and initiation of treatment modalities can be based.
Spinocerebellar ataxia type 17; Dementia; Short CAG repeat expansion
Results 1-3 (3)
Go to page number:
Remove citation from clipboard
Add citation to clipboard
This will clear all selections from your clipboard. Do you wish proceed?
Clipboard is full! Please remove an item and try again.
PubMed Central Canada is a service of the
Canadian Institutes of Health Research
(CIHR) working in partnership with the National Research Council's
national science library
in cooperation with the
National Center for Biotechnology Information
U.S. National Library of Medicine
(NCBI/NLM). It includes content provided to the
PubMed Central International archive
by participating publishers.