Research Topics
Genomes and Genes
| Christine Van BroeckhovenSummaryAffiliation: University of Antwerp Country: Belgium Publications
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Detail Information
Publications
Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer diseaseN Brouwers
VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp Campus CDE, Universiteitsplein 1, B 2610 Antwerpen, Belgium
Neurology 71:656-64. 2008..We assessed whether PGRN also contributes to genetic risk for Alzheimer disease (AD) in an extended Belgian AD patient group (n = 779, onset age 74.7 +/- 8.7 years)...
Genetics and pathology of alpha-secretase site AbetaPP mutations in the understanding of Alzheimer's diseaseChristine Van Broeckhoven
Department of Molecular Genetics, Neurodegenerative Brain Diseases Research Group, Flanders Interuniversity Institute for Biotechnology, Institute Born Bunge and University of Antwerp, Antwerpen, Belgium
J Alzheimers Dis 9:389-98. 2006..In addition, this review will also point directions that warrant additional studies...
Alzheimer and Parkinson diagnoses in progranulin null mutation carriers in an extended founder familyNathalie Brouwers
VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp CDE, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
Arch Neurol 64:1436-46. 2007..Progranulin gene (PGRN) haploinsufficiency was recently associated with ubiquitin-positive frontotemporal lobar degeneration linked to chromosome 17q21 (FTLDU-17)...
Association of brain-specific tryptophan hydroxylase, TPH2, with unipolar and bipolar disorder in a Northern Swedish, isolated populationAnn Van Den Bogaert
Applied Molecular Genomics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
Arch Gen Psychiatry 63:1103-10. 2006..Tryptophan hydroxylase 2 (TPH2) was found to be solely expressed in the brain and therefore considered an important susceptibility gene in psychiatric disorders...
Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in recurrent major depressive disorderFilip Van Den Eede
Department of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
Psychiatry Res 153:17-25. 2007..The association between genetic CRF-BP variants and MDD may be sexually dimorphic, but this issue requires further investigation in a larger sample...
TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohortJulie van der Zee
Neurodegenerative Brain Disease Group, VIB Department of Molecular Genetics, University of Antwerp CDE, Universiteitsplein 1, 2610 Antwerpen, Belgium
Brain 134:808-15. 2011..Additional studies are needed to unravel the molecular role of TMEM106B in disease onset and pathogenesis...
Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian populationKaren Nuytemans
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Hum Mutat 30:1054-61. 2009..Furthermore, though mutations is SNCA, PINK1, and PARK7 are rare, our identification of a SNCA duplication confirmed that screening of these genes remains meaningful...
Follow-up study of susceptibility loci for Alzheimer's disease and onset age identified by genome-wide associationKarolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
J Alzheimers Dis 19:1169-75. 2010..90; nominal p = 0.01)). Overall, our data provided independent support for association of at least one chromosomal locus with AD and warranted a more in-depth investigation of these regions for possible underlying functional variants...
Progranulin expression correlates with dense-core amyloid plaque burden in Alzheimer disease mouse modelsSandra Pereson
Department of Molecular Genetics, VIB, Antwerpen, Belgium
J Pathol 219:173-81. 2009..Because loss of GRN has recently been shown to cause frontotemporal dementia and serves as a risk factor for AD, the strong GRN reactivity around dense-core plaques is consistent with an important role of this factor in AD pathogenesis...
Single nucleotide polymorphism analysis of corticotropin-releasing factor-binding protein gene in bipolar disorderFilip Van Den Eede
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium
Psychiatr Genet 17:304-7. 2007..In conclusion, this study in an isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder...
Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patientsKaren Nuytemans
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Eur J Hum Genet 16:471-9. 2008..Functional data should underlie a conclusion on the pathogenic nature of some mutations that have not been conclusively linked to disease...
Contribution of TARDBP to Alzheimer's disease genetic etiologyNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
J Alzheimers Dis 21:423-30. 2010..In conclusion, the genetic contribution of TARDBP to AD was restricted to the rare mutation p.Ala90Val (3/739, 0.4%) of unclear pathogenic nature that affects the nuclear localization signal in TDP-43...
Intraneuronal amyloid beta and reduced brain volume in a novel APP T714I mouse model for Alzheimer's diseaseBianca Van Broeck
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
Neurobiol Aging 29:241-52. 2008..These data support earlier observations of A beta accumulation in the endosomal-lysosomal pathway and the hypothesis that intraneuronal accumulation of A beta could be an important factor in the AD pathogenesis...
Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation updateKaren Nuytemans
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Hum Mutat 31:763-80. 2010....
DNMBP is genetically associated with Alzheimer dementia in the Belgian populationKarolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein 1, 2610 Antwerpen, Belgium
Neurobiol Aging 30:2000-9. 2009..Taken together our findings underscore a role for DNMBP in the genetic risk for late-onset AD in the Belgian population...
Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's diseaseNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics Flanders Interuniversity Institute for Biotechnology Antwerpen, Belgium
Brain 129:2984-91. 2006....
A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLDJulie van der Zee
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
Brain 129:841-52. 2006..Together, these results strongly suggest that the DR2-DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations...
No association between CALHM1 and risk for Alzheimer dementia in a Belgian populationKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerpen, Belgium
Hum Mutat 30:E570-4. 2009..Despite its functional properties, our study suggests the polymorphism does not contribute significantly to AD risk in the Belgian population...
Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sampleRosa Rademakers
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
Am J Hum Genet 77:643-52. 2005....
Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21Marc Cruts
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
Nature 442:920-4. 2006..Furthermore, in a Belgian series of familial FTD patients, PGRN mutations were 3.5 times more frequent than mutations in MAPT, underscoring a principal involvement of PGRN in FTD pathogenesis...
Mutations other than null mutations producing a pathogenic loss of progranulin in frontotemporal dementiaJulie van der Zee
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Hum Mutat 28:416. 2007..Our findings extend the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for FTD...
Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40Samir Kumar-Singh
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology, University of Antwerp, Antwerpen, Belgium
Hum Mutat 27:686-95. 2006..Also, the in vitro method we describe here is a valid tool for assaying the pathogenic potential of clinical PSEN mutations in a molecular diagnostic setting...
No association of CSF biomarkers with APOEepsilon4, plaque and tangle burden in definite Alzheimer's diseaseSebastiaan Engelborghs
Department of Neurology and Memory Clinic, Middelheim General Hospital ZNA, Antwerpen, Belgium
Brain 130:2320-6. 2007....
Common variation in GRB-associated Binding Protein 2 (GAB2) and increased risk for Alzheimer dementiaKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp CDE, Universiteitsplein 1, B 2610 Antwerpen, Belgium
Hum Mutat 30:E338-44. 2009..6). The association was driven by a higher frequency of the major haplotype in patients. Our data independently replicate an association between GAB2 and late-onset AD, which appears to be limited to APOE epsilon4 carriers...
Characterization of ubiquitinated intraneuronal inclusions in a novel Belgian frontotemporal lobar degeneration familyDaniel Pirici
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB8, Institute Born-Bunge, University of Antwerp, Belgium
J Neuropathol Exp Neurol 65:289-301. 2006..Whereas the precise nature of the protein remains elusive, characterization of such familial FTLD-U patients would be helpful in identifying a common denominator in the pathogenesis of familial and the more prevalent sporadic FTLD-U...
Comprehensive genetic and mutation analysis of familial dementia with Lewy bodies linked to 2q35-q36Bram Meeus
Department of Molecular Genetics, VIB, Antwerpen, Belgium
J Alzheimers Dis 20:197-205. 2010..Nevertheless, identifying the first familial DLB gene is likely to contribute an entry point into the pathogenic cascades underlying DLB pathology...
CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitroJulie van der Zee
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Hum Mol Genet 17:313-22. 2008..We also describe a missense mutation in exon 5 of CHMP2B (p.Asn143Ser) in a familial patient with cortical basal degeneration. However, the pathogenic character of this mutation remains elusive...
Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson diseaseVeerle Bogaerts
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Hum Mutat 29:832-40. 2008..The latter underpins a previously unrecognized role for altered HTRA2 expression as a risk factor relevant to parkinsonian neurodegeneration...
A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification studyIlse Gijselinck
Department of Molecular Genetics, VIB, Antwerp, Belgium
Lancet Neurol 11:54-65. 2012..A locus on chromosome 9p21 has been associated with both disorders, and we aimed to identify the causal gene within this region...
Promoter mutations that increase amyloid precursor-protein expression are associated with Alzheimer diseaseJessie Theuns
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, University of Antwerp, Antwerpen, Belgium
Am J Hum Genet 78:936-46. 2006..The present study provides evidence that APP-promoter mutations that significantly increase APP expression levels are associated with AD...
Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depressionDirk van West
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp, Antwerp, Belgium
Neuropsychopharmacology 31:620-7. 2006..This study suggests that polymorphisms in the 5' region of the NR3C1 gene may play a role in the genetic vulnerability for MDD...
Serum biomarker for progranulin-associated frontotemporal lobar degenerationKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB Flanders Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium
Ann Neurol 65:603-9. 2009..Mutations that lead to a loss of progranulin (PGRN) explain a considerable portion of the occurrence of frontotemporal lobar degeneration. We tested a biomarker allowing rapid detection of a loss of PGRN...
GIGYF2 has no major role in Parkinson genetic etiology in a Belgian populationBram Meeus
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, B 2610 Antwerpen, Belgium
Neurobiol Aging 32:308-12. 2011..Together, our results do not support a role for GIGYF2 in the genetic etiology of Belgian PD...
novoSNP, a novel computational tool for sequence variation discoveryStefan Weckx
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
Genome Res 15:436-42. 2005....
A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorderVeerle Bogaerts
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Institute Born Bunge, Antwerpen, Belgium
Brain 130:2277-91. 2007..Once identified this will be the first novel causal gene for DLB and can be expected to open new avenues for biological studies of the disease process...
Neuronal inclusion protein TDP-43 has no primary genetic role in FTD and ALSIlse Gijselinck
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Belgium
Neurobiol Aging 30:1329-31. 2009..Our data implicate that TDP-43 has no primary genetic role in the pathophysiological mechanisms underlying central nervous system neurodegeneration in these diseases...
SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian populationKarolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Antwerpen, Belgium
Hum Mutat 29:769-70. 2008..Our findings confirm that genetic variants in SORL1 may be important risk factors for late-onset AD...
TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degenerationHans Wils
Department of Molecular Genetics, VIB, B 2610 Antwerpen, Belgium
Proc Natl Acad Sci U S A 107:3858-63. 2010..These findings suggest that approximately 25-kDa TDP-43 CTFs are noxious to neurons by a gain of aberrant nuclear function...
Reduced brain volumes in mice expressing APP-Austrian mutation but not in mice expressing APP-Swedish-Austrian mutationsBianca Van Broeck
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Neurosci Lett 447:143-7. 2008..These data also provide a first in vivo indication of altered processing of APP-Swedish at sub-endogenous levels, an effect not observed in mouse models expressing the APP-Swedish mutation in high amounts...
Frontotemporal lobar degeneration with ubiquitin-positive inclusions: a molecular genetic updateJulie van der Zee
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Laboratory of Neurogenetics, Institute Born Bunge, and University of Antwerp, Antwerp, Belgium
Neurodegener Dis 4:227-35. 2007..This review focuses on the molecular genetic processes underlying FTLD-U pathology...
Genetic variant in the HSPB1 promoter region impairs the HSP27 stress responseInes Dierick
Peripheral Neuropathy Group, University of Antwerp, Universiteitsplein 1, Antwerpen, Belgium
Hum Mutat 28:830. 2007..Therefore, our study suggests that the functional HSPB1 variant may represent a genetic modifier in the pathogenesis of motor neuron disease; however, it is necessary to confirm this HSPB1 variant in additional ALS patients...
Increased caspase activation and decreased TDP-43 solubility in progranulin knockout cortical culturesGernot Kleinberger
Department of Molecular Genetics, VIB, Universiteitsplein 1, Antwerpen, Belgium
J Neurochem 115:735-47. 2010..This leads to increased aggregation and accumulation of full-length TDP-43 along with its C-terminal derivatives by both caspase-dependent and independent mechanisms...
High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsyRosa Rademakers
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
Hum Mol Genet 14:3281-92. 2005..Thus, risk variants on different H1 htSNP haplotypes and protective variants on H2 contribute to population risk for PSP...
Genomewide scan for affective disorder susceptibility Loci in families of a northern Swedish isolated populationTine Venken
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB, University of Antwerp, Antwerp, Belgium
Am J Hum Genet 76:237-48. 2005..These results suggest a susceptibility locus on 9q31-q33 for affective disorder in this common ancestral region...
No allelic association or interaction of three known functional polymorphisms with bipolar disorder in a northern Swedish isolated populationAnn Van Den Bogaert
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium
Psychiatr Genet 16:209-12. 2006....
Genomic architecture of human 17q21 linked to frontotemporal dementia uncovers a highly homologous family of low-copy repeats in the tau regionMarc Cruts
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
Hum Mol Genet 14:1753-62. 2005..The presence of multiple homologous LCRs in the region predicts that other potentially more complex genomic rearrangements might be underlying FTDU-17...
The UBQLN1 polymorphism, UBQ-8i, at 9q22 is not associated with Alzheimer's disease with onset before 70 yearsNathalie Brouwers
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology and Institute Born Bunge, University of Antwerp, Universiteitsplein 1, Belgium
Neurosci Lett 392:72-4. 2006..Our study does not support a major role for this UBQLN1 polymorphism in AD patients with an earlier onset of disease...
A novel presenilin 1 mutation associated with Pick's disease but not beta-amyloid plaquesBart Dermaut
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology VIB8, University of Antwerp, Antwerpen, Belgium
Ann Neurol 55:617-26. 2004..Our results suggest PS1 as a candidate gene for Pick-type tauopathy without MAPT mutations...
Tau is central in the genetic Alzheimer-frontotemporal dementia spectrumBart Dermaut
Department of Molecular Genetics (VIB 8, Flanders Interuniversity Institute for Biotechnology, Neurodegenerative Brain Diseases Group, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B-2610 Antwerpen, Belgium
Trends Genet 21:664-72. 2005..Together, these studies suggest that AD and FTD are linked in a genetic spectrum of presenile degenerative brain disorders in which tau appears to be the central player...
Alzheimer-associated C allele of the promoter polymorphism -22C>T causes a critical neuron-specific decrease of presenilin 1 expressionJessie Theuns
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
Hum Mol Genet 12:869-77. 2003..Together, these studies provide evidence that the increased risk for AD associated with PSEN1 may result from genetic variations in the regulatory region, leading to altered expression levels of PSEN1 in neurons...
APP and BACE1 miRNA genetic variability has no major role in risk for Alzheimer diseaseKarolien Bettens
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Hum Mutat 30:1207-13. 2009..033). While the exact role of the patient-specific miRNA variants within the 3' UTR region of APP and BACE1 demands further analyses, this study does not support a major contribution of miRNA genetic variability to AD pathogenesis...
Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approachesBianca Van Broeck
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, University of Antwerp, Universiteitsplein I, BE 2610 Antwerp, Belgium
Neurodegener Dis 4:349-65. 2007..Secondly, considering these mechanistic insights, we will discuss some therapeutic strategies which are currently in clinical or preclinical trials for AD...
Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel wallsSamir Kumar-Singh
Department of Molecular Genetics VIB8, Neurodegenerative Brain Diseases Research Group, Molecular Neuropathology Project, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
Am J Pathol 167:527-43. 2005....
SNPbox: web-based high-throughput primer design with an eye for repetitive sequencesStefan Weckx
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, University of Antwerp, Belgium
Methods Mol Biol 402:179-200. 2007..SNPbox.org, and explain how pre-designed primers for Ensembl genes can be visualized and retrieved...
SNPbox: a modular software package for large-scale primer designStefan Weckx
Department of Molecular Genetics, Bioinformatics Unit, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium
Bioinformatics 21:385-7. 2005..Of the 2500 primer sets designed by SNPbox, 95% successfully amplified genomic DNA under uniform PCR conditions. AVAILABILITY: The software is available from the authors upon request. SUPPLEMENTARY INFORMATION: SNPbox_supplement...
Ataxin-2 polyQ expansions in FTLD-ALS spectrum disorders in Flanders-Belgian cohortsTim Van Langenhove
Department of Molecular Genetics, VIB, Universiteitsplein 1, Antwerpen, Belgium
Neurobiol Aging 33:1004.e17-20. 2012..Our results provide further support to the notion that ATXN2 associated polyglutamine amplification is specific to the ALS-end of the FTLD-ALS disease spectrum...
alpha-Synuclein promoter confers susceptibility to Parkinson's diseasePhilippe Pals
Department of Molecular Genetics VIB8, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
Ann Neurol 56:591-5. 2004..3kb of sequence, which is overrepresented in patients. Our findings represent a biomarker for PD and may have implications for patient diagnosis, longitudinal evaluation, and treatment...
DLB and PDD: a role for mutations in dementia and Parkinson disease genes?Bram Meeus
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Neurobiol Aging 33:629.e5-629.e18. 2012..They do support the hypothesis of a genetic overlap between members of the Lewy body disease spectrum, but additional genes still have to exist...
The corticotropin-releasing hormone binding protein is associated with major depression in a population from Northern SwedenStephan Claes
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Belgium
Biol Psychiatry 54:867-72. 2003..Therefore, the gene encoding for corticotropin releasing hormone binding protein is a functional candidate gene for major depression...
Molecular genetics of Alzheimer's disease: an updateNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
Ann Med 40:562-83. 2008..This review provides an overview of the current understanding in the field of AD genetics, covering both the rare monogenic forms as well as recent developments in the search for novel AD susceptibility genes...
Molecular pathways of frontotemporal lobar degenerationKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Universiteitsplein 1, B 2610 Antwerpen, Belgium
Annu Rev Neurosci 33:71-88. 2010..g., the role of FUS in amyotrophic lateral sclerosis...
PRNP Val129 homozygosity increases risk for early-onset Alzheimer's diseaseBart Dermaut
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology VIB8, University of Antwerp, Antwerpen, Belgium
Ann Neurol 53:409-12. 2003..2; 95% CI, 1.4-7.1; p < 0.01). In patients with a positive family history, these risks increased to 2.6 (95% CI, 1.3-5.3; p < 0.01) and 3.5 (95% CI, 1.3-9.3; p = 0.01), respectively...
Associations between common arginine vasopressin 1b receptor and glucocorticoid receptor gene variants and HPA axis responses to psychosocial stress in a child psychiatric populationDirk van West
Department of Molecular Genetics, Applied Molecular Genomics Group, VIB, Belgium
Psychiatry Res 179:64-8. 2010..However, the small number of ER22/23EK subjects does not allow us to draw definitive conclusions about the genotypic effect...
Progranulin genetic variability contributes to amyotrophic lateral sclerosisK Sleegers
Neurodegenerative Brain Diseases Group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
Neurology 71:253-9. 2008..Here we examined PGRN genetic variability in amyotrophic lateral sclerosis (ALS), a neurodegenerative motor neuron disease that overlaps with FTD at a clinical, pathologic, and epidemiologic level...
In vitro studies of Flemish, Dutch, and wild-type beta-amyloid provide evidence for two-staged neurotoxicitySamir Kumar-Singh
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, University of Antwerp, B-2610 Antwerp, Belgium
Neurobiol Dis 11:330-40. 2002....
Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathyGert Van Goethem
Neuromuscular Reference Center and Department of Neurology, University Hospital of Antwerp UZA, Antwerpen, Belgium
Eur J Hum Genet 11:547-9. 2003..The third mutation was previously reported as a recessive POLG mutation (T251I). This finding indicates the need for POLG sequencing in patients with features of MNGIE without TP mutations...
Frontotemporal lobar degeneration: current concepts in the light of recent advancesSamir Kumar-Singh
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Laboratory of Neurogenetics, VIB, Institute Born Bunge and University of Antwerp, BE 2610 Antwerpen, Belgium
Brain Pathol 17:104-14. 2007..These findings are pivotal for dissecting the pathways by which different etiologies lead to the varied clinicopathological presentations of FTLD...
Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentricSamir Kumar-Singh
Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium
Am J Pathol 161:507-20. 2002....
Progressive external ophthalmoplegia and multiple mitochondrial DNA deletionsGert Van Goethem
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB 8, University of Antwerp UIA
Acta Neurol Belg 102:39-42. 2002..We also identified POLG mutations in two families with arPEO, which underlines the crucial role of the mtDNA replication machinery for mtDNA maintenance...
Progressive external ophthalmoplegia characterized by multiple deletions of mitochondrial DNA: unraveling the pathogenesis of human mitochondrial DNA instability and the initiation of a genetic classificationGert Van Goethem
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB, Born-Bunge Foundation (BBS, University of Antwerp (UIA, Antwerpen, Belgium
Neuromolecular Med 3:129-46. 2003..Since clinical presentations are heterogeneous and overlap with different previously described clinical syndromes, we advocate the use of a genetic, instead of a clinical, classification of disorders with multiple mtDNA deletions...
The gene encoding nicastrin, a major gamma-secretase component, modifies risk for familial early-onset Alzheimer disease in a Dutch population-based sampleBart Dermaut
Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, B 2610 Antwerpen, Belgium
Am J Hum Genet 70:1568-74. 2002..1; 95% confidence interval 1.2-13.3; P=.01). These results are compatible with an important role of gamma-secretase dysfunction in the etiology of familial EOAD...
Genetics of early-onset Alzheimer dementiaRosa Rademakers
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB, University of Antwerp, Antwerpen, Belgium
ScientificWorldJournal 3:497-519. 2003..Now, transgenic mice are produced to study the influence of EOAD mutations in vivo, eventually leading to the development of novel therapeutic strategies...
A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheathsEva Nelis
Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology VIB, Born Bunge Foundation BBS, University of Antwerp UIA, Antwerp, Belgium
Neuromuscul Disord 12:869-73. 2002..This is the second homozygous missense mutation associated with recessive Charcot-Marie-Tooth disease with focally folded myelin sheaths...
Invited article: the Alzheimer disease-frontotemporal lobar degeneration spectrumJulie van der Zee
VIB Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, University of Antwerp CDE, Universiteitsplein 1, B 2610, Belgium
Neurology 71:1191-7. 2008..Herein, we focus on recent exciting findings providing further support for an AD-FTLD spectrum...
De novo SCN1A mutations are a major cause of severe myoclonic epilepsy of infancyLieve Claes
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, Born Bunge Foundation, University of Antwerp UIA, Antwerpen, Belgium
Hum Mutat 21:615-21. 2003..In contrast to our previous study, most mutations are missense mutations clustering in the S4-S6 region of SCN1A. These findings demonstrate that de novo mutations in SCN1A are a major cause of isolated SMEI...
Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathyJoy Irobi
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Universiteitsplein 1, B 2610 Antwerpen, Belgium
Nat Genet 36:597-601. 2004..Expression of mutant HSPB8 in cultured cells promoted formation of intracellular aggregates. Our findings provide further evidence that mutations in heat-shock proteins have an important role in neurodegenerative disorders...
Loss of progranulin function in frontotemporal lobar degenerationMarc Cruts
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Trends Genet 24:186-94. 2008..The high variability in onset age and age-dependent penetrance suggests that the PGRN pathway is highly susceptible to modulating factors that might be exploited to delay the disease processes...
Genome-wide linkage of febrile seizures and epilepsy to the FEB4 locus at 5q14.3-q23.1 and no MASS1 mutationLiesbet Deprez
Neurogenetics Group, Department of Molecular Genetics VIB8, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerpen, Belgium
Hum Genet 118:618-25. 2006..However, our mutation data is negative and do not support a role for MASS1 suggesting that another gene within or near the FEB4 locus might exist...
Alzheimer dementia caused by a novel mutation located in the APP C-terminal intracytosolic fragmentJ Theuns
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Belgium
Hum Mutat 27:888-96. 2006..Further, in vivo amyloid positron emission tomography (PET) imaging revealed significantly increased cortical amyloid deposits, supporting that in human this novel APP mutation is likely causing disease...
Mutation analysis of 12 candidate genes for distal hereditary motor neuropathy type II (distal HMN II) linked to 12q24.3Joy Irobi
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB, Born Bunge Foundation BBS, University of Antwerp, Antwerpen, Belgium
J Peripher Nerv Syst 7:87-95. 2002....
Current status on Alzheimer disease molecular genetics: from past, to present, to futureKarolien Bettens
Department of Molecular Genetics, Institute Born Bunge, University of Antwerp, Antwerpen, Belgium
Hum Mol Genet 19:R4-R11. 2010....
Molecular pathogenesis of frontotemporal lobar degeneration: basic science seminar in neurologyKristel Sleegers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Institute for Biotechnology, Flanders, and Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
Arch Neurol 65:700-4. 2008
Genes and loci involved in febrile seizures and related epilepsy syndromesDominique Audenaert
Department of Molecular Genetics, Neurogenetics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
Hum Mutat 27:391-401. 2006..We also discuss the knowledge we currently have and hypotheses regarding the effect of the mutations on their respective protein functions...
Progranulin mutations in ubiquitin-positive frontotemporal dementia linked to chromosome 17q21Marc Cruts
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Curr Alzheimer Res 3:485-91. 2006..These findings open promising novel targets for therapeutic intervention against neurodegeneration...
Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/TwinkleGert Van Goethem
Hum Mutat 22:175-6. 2003
Progranulin null mutations in both sporadic and familial frontotemporal dementiaIsabelle Le Ber
INSERM, UMR679, Paris, France
Hum Mutat 28:846-55. 2007..Taking this into account, genetic testing should be now considered more systematically, even in patients without obvious familial history of FTD...
A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch populationFan Liu
Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics and Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
Am J Hum Genet 81:17-31. 2007..For this region, our analysis identified the NMNAT3 and CLSTN2 genes. Our findings confirm linkage to chromosome 11q25. We were unable to confirm SORL1; instead, our analysis points to the OPCML and HNT genes...
Genetic testing has no place as a routine diagnostic test in sporadic and familial cases of Alzheimer's diseaseTischa J M van der Cammen
Memory Clinic, Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
J Am Geriatr Soc 52:2110-3. 2004..Arguments as to why we think routine genetic assessment should not be part of the diagnostic examination of the patient suspected of Alzheimer's disease are given...
VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic deathDiether Lambrechts
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology and Department of Neurology, University Hospital Gasthuisberg, KU Leuven, Leuven, B 3000, Belgium
Nat Genet 34:383-94. 2003..These findings indicate that VEGF is a modifier of motoneuron degeneration in human ALS and unveil a therapeutic potential of Vegfa for stressed motoneurons in mice...
Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriersJohanna Lind
Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N 8, Stockholm, Sweden
Brain 129:1240-8. 2006..Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level...
Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson diseaseDemetrius M Maraganore
Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA
JAMA 296:661-70. 2006..Alpha-synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking...
Non-replication of the brain-derived neurotrophic factor (BDNF) association in bipolar affective disorder: a Belgian patient-control studyPierre Oswald
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Brussels, Belgium
Am J Med Genet B Neuropsychiatr Genet 129:34-5. 2004..44). We failed to replicate previous findings implicating BDNF in the aetiology of BPAD. However, BDNF remains an interesting target for future genetic studies and should be tested in prospective pharmacogenetic therapeutic trials...
Twinkle and POLG defects enhance age-dependent accumulation of mutations in the control region of mtDNASjoerd Wanrooij
Institute of Medical Technology and Tampere University Hospital, Tampere, Finland
Nucleic Acids Res 32:3053-64. 2004..Deletion breakpoint analysis showed frequent breakpoints around homopolymeric runs, which could be a signature of replication stalling. Therefore, we propose replication stalling as the principal cause of deletion formation...
Novel APP mutation V715A associated with presenile Alzheimer's disease in a German familyMarc Cruts
J Neurol 250:1374-5. 2003
Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob diseaseEsther A Croes
Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands
Eur J Hum Genet 12:389-94. 2004....
Cyclin-dependent kinase 5 is associated with risk for Alzheimer's disease in a Dutch population-based studyAlejandro Arias-Vasquez
Genetic Epidemiology Unit, Dept of Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
J Neurol 255:655-62. 2008..In our analysis, the haplotype tagged by the G allele of SNP rs2069442 was significantly associated with AD (p = 0.05). In conclusion, our study suggests that CDK5 may be associated with AD...
Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementiaSebastiaan Engelborghs
Department of Neurology and Memory Clinic, Middelheim General Hospital, ZNA, Antwerp, Belgium
Neurobiol Aging 27:285-92. 2006..In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB)...
APP duplication is sufficient to cause early onset Alzheimer's dementia with cerebral amyloid angiopathyKristel Sleegers
Neurodegenerative Brain Diseases Group Antwerp, Belgium
Brain 129:2977-83. 2006..Our findings corroborated a recent French study, and indicated that investigating genomic duplications in the APP locus in families segregating Alzheimer's disease and CAA should be considered...
Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic studyIsabelle Le Ber
1INSERM, UMR_S679 Neurologie and Thérapeutique Expérimentale, F 75013, Paris, France
Brain 131:732-46. 2008..Since all the mutations cause a progranulin haploinsufficiency, additional factors probably explain the variable clinical presentation of the disease...
Association study of cholesterol-related genes in Alzheimer's diseaseM Axel Wollmer
Division of Psychiatry Research, University of Zurich, August Forel Str 1, 8008 Zurich, Switzerland
Neurogenetics 8:179-88. 2007..004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples...
Visualization of MAPT inversion on stretched chromosomes of tau-negative frontotemporal dementia patientsIlse Gijselinck
Hum Mutat 27:1057-9. 2006
