| 1. |
|
|
| 2. |
|
|
| 3. |
- Rademakers, Rosa, et al.
(författare)
-
Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:2, s. 200-5
-
Tidskriftsartikel (refereegranskat)abstract
- Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.
|
|
| 4. |
- Kristoffersen, Agnete E., et al.
(författare)
-
Consultations with health care providers and use of self-management strategies for prevention and treatment of COVID-19 related symptoms. A population based cross-sectional study in Norway, Sweden and the Netherlands
- 2022
-
Ingår i: Complementary Therapies in Medicine. - : Elsevier. - 0965-2299 .- 1873-6963. ; 64
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The present study was initiated to determine consultations with health care providers and use of self-management strategies for prevention or treatment of COVID-19 related symptoms in countries with a full lockdown (Norway), a partial lockdown (the Netherlands) and no lockdown (Sweden) during the first three months of the COVID-19 pandemic, and if such use correlates with worries of being infected by COVID-19 disease.Design: Data were collected in collaboration with Ipsos A/S in April-June 2020. An adapted version of the International Questionnaire to measure use of Complementary and Alternative Medicine (I-CAM-Q) was used with the categories “for prevention of COVID-19” and “to treat COVID-19-related symptoms” added. Data were collected among a representative sample in Norway, Sweden and the Netherlands using data assisted telephone interviews (Norway, n=990 and Sweden, n=500), and an online survey (the Netherlands, n=1004). Total response rate was 30%.Results: Very few consulted a health care provider with the intention to treat or prevent COVID-19 (1.2% and 1.0% respectively) with medical doctors mostly visited (1.0% and 0.9% respectively). Similarly, the use of self-management strategies to prevent or treat COVID-19 was low (3.4% and 0.2% respectively); most commonly used for prevention of COVID-19 were vitamins and minerals (2.8%). Consultations with health care providers and use of self-management strategies for prevention of COVID-19 were positively associated with worries of being infected with COVID-19.Conclusions: The COVID-19 pandemic does not seem to have evoked a large-scale difference in behavior related to consultations with health care providers or the use of self-management strategies in any of the three countries.
|
|
| 5. |
- Sundal, Christina, et al.
(författare)
-
Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations
- 2013
-
Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020. ; 19:10, s. 869-877
-
Tidskriftsartikel (refereegranskat)abstract
- Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by noninflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We studied neuropathologically verified HDLS patients with CSF1R mutations to assess parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18-71) and the mean disease duration was approximately six years (range, 3-11). We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations.
|
|
| 6. |
- Vilarino-Gueell, Carles, et al.
(författare)
-
VPS35 Mutations in Parkinson Disease
- 2011
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 89:1, s. 162-167
-
Tidskriftsartikel (refereegranskat)abstract
- The identification of genetic causes for Mendelian disorders has been based on the collection of multi-incident families, linkage analysis, and sequencing of genes in candidate intervals. This study describes the application of next-generation sequencing technologies to a Swiss kindred presenting with autosomal-dominant, late-onset Parkinson disease (PD). The family has tremor-predominant dopa-responsive parkinsonism with a mean onset of 50.6 +/- 7.3 years. Exome analysis suggests that an aspartic-acid-to-asparagine mutation within vacuolar protein sorting 35 (VPS35 c.1858G>A; p.Asp620Asn) is the genetic determinant of disease. VPS35 is a central component of the retromer cargo-recognition complex, is critical for endosome-trans-golgi trafficking and membrane-protein recycling, and is evolutionarily highly conserved. VPS35 c.1858G>A was found in all affected members of the Swiss kindred and in three more families and one patient with sporadic PD, but it was not observed in 3,309 controls. Further sequencing of familial affected probands revealed only one other missense variant, VPS35 c.946C>T; (p.Pro316Ser), in a pedigree with one unaffected and two affected carriers, and thus the pathogenicity of this mutation remains uncertain. Retromer-mediated sorting and transport is best characterized for acid hydrolase receptors. However, the complex has many types of cargo and is involved in a diverse array of biologic pathways from developmental Wnt signaling to lysosome biogenesis. Our study implicates disruption of VPS35 and retromer-mediated trans-membrane protein sorting, rescue, and recycling in the neurodegenerative process leading to PD.
|
|
