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Birve, Anna
Publikasjoner (10 av 33) Visa alla publikasjoner
Keskin, I., Birve, A., Berdynski, M., Hjertkvist, K., Rofougaran, R., Nilsson, T. K., . . . Andersen, P. M. (2017). Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 18(5-6), 457-463
Åpne denne publikasjonen i ny fane eller vindu >>Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives
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2017 (engelsk)Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 5-6, s. 457-463Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective: To characterise stabilities in erythrocytes of mutant SOD1 proteins, compare SOD1 enzymatic activities between patients with different genetic causes of ALS and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations.Methods: Blood samples from 4072 individuals, ALS patients with or without a SOD1 mutation, family members and controls were studied. Erythrocyte SOD1 enzymatic activities normalised to haemoglobin content were determined, and effects of haemoglobin disorders on dismutation assessed. Coding SOD1 sequences were analysed by Sanger sequencing, exon copy number variations by fragment length analysis and by TaqMan Assay.Results: Of the 44 SOD1 mutations found, 75% caused severe destabilisation of the mutant protein but in 25% it was physically stable. Mutations producing structural changes caused halved erythrocyte SOD1 activities. There were no differences in SOD1 activities between patients without a SOD1 mutation and control individuals or carriers of TBK1 mutations and C9orf72(HRE). In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Thalassemias and iron deficiency were associated with increased SOD1 activity/haemoglobin ratios.Conclusion: Adjunct erythrocyte SOD1 activity analysis reliably signals destabilising SOD1 mutations including intronic mutations that are missed by exon sequencing.

sted, utgiver, år, opplag, sider
TAYLOR & FRANCIS LTD, 2017
Emneord
Amyotrophic lateral sclerosis, superoxide dismutase, mutation, enzymatic activity
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-138241 (URN)10.1080/21678421.2017.1301481 (DOI)000405584600019 ()
Tilgjengelig fra: 2017-08-16 Laget: 2017-08-16 Sist oppdatert: 2018-06-09bibliografisk kontrollert
Ingre, C., Wuolikainen, A., Marklund, S. L., Birve, A., Press, R. & Andersen, P. M. (2016). A 50bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 17(5-6), 452-457
Åpne denne publikasjonen i ny fane eller vindu >>A 50bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden
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2016 (engelsk)Inngår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 17, nr 5-6, s. 452-457Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population.

Emneord
ALS, SOD1, promoter, deletion, age of onset, disease duration
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-127984 (URN)10.3109/21678421.2016.1159223 (DOI)000381024500019 ()27002425 (PubMedID)
Tilgjengelig fra: 2016-12-05 Laget: 2016-11-21 Sist oppdatert: 2019-05-09bibliografisk kontrollert
Keskin, I., Forsgren, E., Lange, D. J., Weber, M., Birve, A., Synofzik, M., . . . Marklund, S. L. (2016). Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients. PLoS ONE, 11(2), Article ID e0150133.
Åpne denne publikasjonen i ny fane eller vindu >>Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients
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2016 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 2, artikkel-id e0150133Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Mutations in superoxide dismutase-1 (SOD1) are a common known cause of amyotrophic lateral sclerosis (ALS). The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.

Emneord
Superoxides, Amyotrophic Lateral Sclerosis
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-118791 (URN)10.1371/journal.pone.0150133 (DOI)000371274400090 ()26919046 (PubMedID)
Tilgjengelig fra: 2016-04-08 Laget: 2016-04-04 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Nordin, A., Akimoto, C., Wuolikainen, A., Alstermark, H., Jonsson, P., Birve, A., . . . Andersen, P. M. (2015). Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD. Human Molecular Genetics, 24(11), 3133-3142
Åpne denne publikasjonen i ny fane eller vindu >>Extensive size variability of the GGGGCC expansion in C9orf72 in both neuronal and non-neuronal tissues in 18 patients with ALS or FTD
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2015 (engelsk)Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 11, s. 3133-3142Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A GGGGCC-repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasians. However, little is known about the variability of the GGGGCC expansion in different tissues and whether this correlates with the observed phenotype. Here, we used Southern blotting to estimate the size of hexanucleotide expansions in C9orf72 in neural and non-neural tissues from 18 autopsied ALS and FTD patients with repeat expansion in blood. Digitalization of the Southern blot images allowed comparison of repeat number, smear distribution and expansion band intensity between tissues and between patients. We found marked intra-individual variation of repeat number between tissues, whereas there was less variation within each tissue group. In two patients, the size variation between tissues was extreme, with repeat numbers below 100 in all studied non-neural tissues, whereas expansions in neural tissues were 20-40 times greater and in the same size range observed in neural tissues of the other 16 patients. The expansion pattern in different tissues could not distinguish between diagnostic groups and no correlation was found between expansion size in frontal lobe and occurrence of cognitive impairment. In ALS patients, a less number of repeats in the cerebellum and parietal lobe correlated with earlier age of onset and a larger number of repeats in the parietal lobe correlated with a more rapid progression. In 43 other individuals without repeat expansion in blood, we find that repeat sizes up to 15 are stable, as no size variation between blood, brain and spinal cord was found.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-103256 (URN)10.1093/hmg/ddv064 (DOI)000355674000011 ()25712133 (PubMedID)
Tilgjengelig fra: 2015-05-19 Laget: 2015-05-19 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Akimoto, C., Volk, A. E., van Blitterswijk, M., Van den Broeck, M., Leblond, C. S., Lumbroso, S., . . . Kubisch, C. (2014). A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories. Journal of Medical Genetics, 51(6), 419-424
Åpne denne publikasjonen i ny fane eller vindu >>A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
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2014 (engelsk)Inngår i: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 51, nr 6, s. 419-424Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-91059 (URN)10.1136/jmedgenet-2014-102360 (DOI)000336841300009 ()
Tilgjengelig fra: 2014-07-11 Laget: 2014-07-10 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Van Doormaal, P. T. C., Ticozzi, N., Gellera, C., Ratti, A., Taroni, F., Chio, A., . . . Veldink, J. H. (2014). Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study. Neurobiology of Aging, 35(10), 2420.e13
Åpne denne publikasjonen i ny fane eller vindu >>Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study
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2014 (engelsk)Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, nr 10, s. 2420.e13-Artikkel i tidsskrift (Fagfellevurdert) Published
sted, utgiver, år, opplag, sider
Elsevier, 2014
Emneord
Amyotrophic lateral sclerosis, Kinesin-associated protein 3 gene, KIFAP3, Genome-wide association study
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-92895 (URN)10.1016/j.neurobiolaging.2014.04.014 (DOI)000339735100031 ()
Tilgjengelig fra: 2014-09-18 Laget: 2014-09-09 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Hugosson, F., Sjögren, C., Birve, A., Hedlund, L., Eriksson, T. & Palmer, R. H. (2014). The Drosophila Midkine/Pleiotrophin Homologues Miple1 and Miple2 Affect Adult Lifespan but Are Dispensable for Alk Signaling during Embryonic Gut Formation. PLoS ONE, 9(11), e112250
Åpne denne publikasjonen i ny fane eller vindu >>The Drosophila Midkine/Pleiotrophin Homologues Miple1 and Miple2 Affect Adult Lifespan but Are Dispensable for Alk Signaling during Embryonic Gut Formation
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2014 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 11, s. e112250-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Midkine (MDK) and Pleiotrophin (PTN) are small heparin-binding cytokines with closely related structures. The Drosophila genome harbours two genes encoding members of the MDK/PTN family of proteins, known as miple1 and miple2. We have investigated the role of Miple proteins in vivo, in particular with regard to their proposed role as ligands for the Alk receptor tyrosine kinase (RTK). Here we show that Miple proteins are neither required to drive Alk signaling during Drosophila embryogenesis, nor are they essential for development in the fruit fly. Additionally we show that neither MDK nor PTN can activate hALK in vivo when ectopically co-expressed in the fly. In conclusion, our data suggest that Alk is not activated by MDK/PTN related growth factors Miple1 and Miple 2 in vivo.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-97588 (URN)10.1371/journal.pone.0112250 (DOI)000344863100069 ()
Tilgjengelig fra: 2015-01-04 Laget: 2014-12-23 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Weishaupt, J. H., Waibel, S., Birve, A., Volk, A. E., Mayer, B., Meyer, T., . . . Andersen, P. M. (2013). A novel optineurin truncating mutation and three glaucoma-associated missense variants in patients with familial amyotrophic lateral sclerosis in Germany. Neurobiology of Aging, 34(5), 1516.e9-1516.e15
Åpne denne publikasjonen i ny fane eller vindu >>A novel optineurin truncating mutation and three glaucoma-associated missense variants in patients with familial amyotrophic lateral sclerosis in Germany
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2013 (engelsk)Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, nr 5, s. 1516.e9-1516.e15Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Mutations in the optineurin (OPTN) gene have been associated with normal tension glaucoma and with amyotrophic lateral sclerosis (ALS). Here, we screened German familial ALS cases for OPTN mutations to gain additional insight into the spectrum and pathogenic relevance of this gene for ALS. One hundred familial German ALS cases and 148 control subjects were screened for OPTN mutations by sequence analysis of the complete OPTN coding sequence, and phenotypes of OPTN mutant patients were described. We identified a novel heterozygous truncating OPTN mutation p.Lys440Asnfs*8 in 1 ALS family with an aggressive ALS disease phenotype. This mutation abolishes protein domains crucial for nuclear factor kappa B signaling. Moreover, we detected 3 different nonsynonymous sequence variants, which have been described previously as risk factors for primary retinal ganglion cell degeneration in normal tension glaucoma. Two of them were detected on the same allele in a family that also carries a p.Asn352Ser disease mutation in the ALS gene TARDBP. All OPTN mutant patients presented with typical spinal onset ALS. Taken together, we detected a novel truncating OPTN mutation associated with an aggressive form of ALS and confirmed that OPTN mutations are a rare cause of ALS. In addition our data suggest that in some cases plausibly more than 1 mutation in OPTN or another ALS gene might be needed to cause ALS. Finally, our findings show that motoneurons and retinal ganglion cells, which are both projecting central nervous system neurons, might share common susceptibility factors. (C) 2013 Elsevier Inc. All rights reserved.

Emneord
Familial ALS, Optineurin, Glaucoma, Retinal degeneration, Truncating mutation
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-67953 (URN)10.1016/j.neurobiolaging.2012.09.007 (DOI)000315729500021 ()
Tilgjengelig fra: 2013-04-15 Laget: 2013-04-09 Sist oppdatert: 2018-06-08bibliografisk kontrollert
Ingre, C., Landers, J. E., Rizik, N., Volk, A. E., Akimoto, C., Birve, A., . . . Weishaupt, J. H. (2013). A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts. Neurobiology of Aging, 34(6), Article ID 1708.e1.
Åpne denne publikasjonen i ny fane eller vindu >>A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts
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2013 (engelsk)Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, nr 6, artikkel-id 1708.e1Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Profilin 1 is a central regulator of actin dynamics. Mutations in the gene profilin 1 (PFN1) have veryrecently been shown to be the cause of a subgroup of amyotrophic lateral sclerosis (ALS). Here, weperformed a large screen of US, Nordic, and German familial and sporadic ALS and frontotemporaldementia (FTLD) patients for PFN1 mutations to get further insight into the spectrum and pathogenicrelevance of this gene for the complete ALS/FTLD continuum. Four hundred twelve familial and 260sporadic ALS cases and 16 ALS/FTLD cases from Germany, the Nordic countries, and the United Stateswere screened for PFN1 mutations. Phenotypes of patients carrying PFN1 mutations were studied. Ina German ALS family we identified the novel heterozygous PFN1 mutation p.Thr109Met, which wasabsent in controls. This novel mutation abrogates a phosphorylation site in profilin 1. The recentlydescribed p.Gln117Gly sequence variant was found in another familial ALS patient from the United States.The ALS patients with mutations in PFN1 displayed spinal onset motor neuron disease without overtcognitive involvement. PFN1 mutations were absent in patients with motor neuron disease anddementia, and in patients with only FTLD. We provide further evidence that PFN1 mutations can causeALS as a Mendelian dominant trait. Patients carrying PFN1 mutations reported so far represent the“classic” ALS end of the ALS-FTLD spectrum. The novel p.Thr109Met mutation provides additional proofof-principle that mutant proteins involved in the regulation of cytoskeletal dynamics can cause motorneuron degeneration. Moreover, this new mutation suggests that fine-tuning of actin polymerization byphosphorylation of profilin 1 might be necessary for motor neuron survival.

sted, utgiver, år, opplag, sider
New York: Elsevier, 2013
Emneord
Amyotrophic lateral sclerosis, ALS, FTLD, profilin1, Cytoskeleton, Actin
HSV kategori
Forskningsprogram
neurologi
Identifikatorer
urn:nbn:se:umu:diva-67457 (URN)10.1016/j.neurobiolaging.2012.10.009 (DOI)000317417100021 ()
Prosjekter
On the aetiology of ALS: A comprehensive genetic study
Tilgjengelig fra: 2013-03-21 Laget: 2013-03-19 Sist oppdatert: 2019-11-19bibliografisk kontrollert
Graffmo, K. S., Forsberg, K., Bergh, J., Birve, A., Zetterström, P., Andersen, P. M., . . . Brännström, T. (2013). Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis. Human Molecular Genetics, 22(1), 51-60
Åpne denne publikasjonen i ny fane eller vindu >>Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis
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2013 (engelsk)Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 22, nr 1, s. 51-60Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

A common cause of amyotrophic lateral sclerosis (ALS) is mutations in the gene encoding superoxide dismutase-1. There is evolving circumstantial evidence that the wild-type protein can also be neurotoxic and that it may more generally be involved in the pathogenesis of ALS. To test this proposition more directly, we generated mice that express wild-type human superoxide dismutase-1 at a rate close to that of mutant superoxide dismutase-1 in the commonly studied G93A transgenic model. These mice developed an ALS-like syndrome and became terminally ill after around 370 days. The loss of spinal ventral neurons was similar to that in the G93A and other mutant superoxide dismutase-1 models, and large amounts of aggregated superoxide dismutase-1 were found in spinal cords, but also in the brain. The findings show that wild-type human superoxide dismutase-1 has the ability to cause ALS in mice, and they support the hypothesis of a more general involvement of the protein in the disease in humans.

HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-63578 (URN)10.1093/hmg/dds399 (DOI)000312643400004 ()23026746 (PubMedID)
Tilgjengelig fra: 2013-01-03 Laget: 2013-01-03 Sist oppdatert: 2018-08-19bibliografisk kontrollert
Organisasjoner