Search

Your search keyword '"Van Camp G"' showing total 168 results
Start Over Author "Van Camp G" Search Limiters Peer Reviewed
168 results on '"Van Camp G"'

3. Antisense oligonucleotides for dominantly inherited hearing impairment DFNA9: from cells models to humanized mice.

Author

Aben, F., Verdoodt, D., de Bruijn, S., Oostrik, J., Venselaar, H., Sels, L., De Backer, E., Gommeren, H., Szewczyk, K., Van Camp, G., Ponsaerts, P., Van Rompaey, V., van Wijk, E., and de Vrieze, E.

Subjects
BIOLOGICAL models, CONFERENCES & conventions, NUCLEOTIDES, MICE, ANIMAL experimentation, HEARING disorders, GENETIC mutation
Abstract

The c.151C>T (p.P51S) mutation in COCH is highly prevalent in the Dutch/Belgian population and causes DFNA9 (hearing loss and vestibular dysfunction) in > 1500 individuals. The initial symptoms manifest between the 3rd and 5th decade of life, which leaves ample time for therapeutic intervention. The clear non-haploinsufficiency disease mechanism indicates that blocking or reducing the p.P51S mutant cochlin protein levels may alleviate or prevent the DFNA9 phenotypes. Considering the broad expression of COCH by the fibrocytes of the inner ear, we designed "gapmer" antisense oligonucleotides (ASO) to specifically induce RNase H1-mediated degradation of COCH transcripts containing the c.151C>T mutation. We established several model systems to investigate the molecular efficacy of ASOs targeting the c. 151C>T mutation or low-frequency mutant allele-specific SNPs. Using overexpression models, we identified several ASOs that efficiently induce the degradation of mutant COCH transcripts. By introducing chemical modification to the oligonucleotide bases, we can alter the affinity and selectivity for the mutation transcript. We identified several ASOs with a strong preference for the mutant transcript in overexpression models. To investigate allele-specificity under physiological expression levels, we exposed patient-derived otic progenitor cells (iPCS-OPCs) to different ASOs for 8 days. In parallel, we developed a genetically humanized mouse model for DFNA9 in which human sequence-specific therapeutic strategies can be evaluated. Phenotypic follow-up of mice of all genotypes indicate that the genetic humanization has no adverse effects, and removal of the Cdh23ahl allele is mandatory to observe the late-onset auditory phenotype: the first signs of high-frequency hearing loss emerged at 12 months of age. Studies in iPSC-OPCs indicated that the ASOs identified in overexpression studies also effectively reduce mutant COCH transcript levels in patient-derived cells with physiological expression levels. Unfortunately, variation between replicate wells of OPC differentiation is relatively high, making it difficult to draw conclusions on allele-specificity. We selected a candidate ASO, directed against a rare mutant allele-spe-cific intronic SNP, for subsequent studies in our humanized mouse model. First intracochlear injections will be conducted in May 2024, after which we can collect the first in vivo data on gapmer ASO uptake and efficacy in fibrocytes of the mammalian inner ear. [ABSTRACT FROM AUTHOR]

Published
2024

26. Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment

Author

Van Eyken, E, Van Camp, G, Fransen, E, Topsakal, V, Hendrickx, J J, Demeester, K, Van de Heyning, P, Mäki-Torkko, E, Hannula, S, Sorri, M, Jensen, M, Parving, A, Bille, M, Baur, M, Pfister, M, Bonaconsa, A, Mazzoli, M, Orzan, E, Espeso, A, Stephens, D, Verbruggen, K, Huyghe, J, Dhooge, I, Huygen, P, Kremer, H, Cremers, C W R J, Kunst, S, Manninen, M, Pyykkö, I, Lacava, A, Steffens, M, Wienker, T F, and Van Laer, L

Published
2007

30. A genotype-phenotype correlation for GJB2 (connexin 26) deafness

Author

Cryns, K, Orzan, E, Murgia, A, Huygen, P L M, Moreno, F, del Castillo, I, Chamberlin, G Parker, Azaiez, H, Prasad, S, Cucci, R A, Leonardi, E, Snoeckx, R L, Govaerts, P J, Van de Heyning, P H, Van de Heyning, C M, Smith, R J H, and Van Camp, G

Published
2004

43. Hotspot DAXX, PTCH2 and CYFIP2 mutations in pancreatic neuroendocrine neoplasms.

Author

Vandamme, T., Beyens, M., Boons, G., Schepers, A., Kamp, K., Biermann, K., Pauwels, P., De Herder, W. W., Hofland, L. J., Peeters, M., Van Camp, G., and de Beeck, K. Op

Subjects
NEUROENDOCRINE tumors, NEUROENDOCRINE system, PARAFFIN test, SINGLE nucleotide polymorphisms, GENE expression
Abstract

Mutations in DAXX/ATRX, MEN1 and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway have been implicated in pancreatic neuroendocrine neoplasms (pNENs). However, mainly mutations present in the majority of tumor cells have been identified, while proliferation-driving mutations could be present only in small fractions of the tumor. This study aims to identify high- and low-abundance mutations in pNENs using ultra-deep targeted resequencing. Formalinfixed paraffin-embedded matched tumor-normal tissue of 38 well-differentiated pNENs was sequenced using a HaloPlex targeted resequencing panel. Novel amplicon-based algorithms were used to identify both single nucleotide variants (SNVs) and insertiondeletions (indels) present in >10% of reads (high abundance) and in <10% of reads (low abundance). Found variants were validated by Sanger sequencing. Sequencing resulted in 416,711,794 reads with an average target base coverage of 26 63 ± 1476. Across all samples, 32 high-abundance somatic, 3 germline and 30 low-abundance mutations were withheld after filtering and validation. Overall, 92% of high-abundance and 84% of low-abundance mutations were predicted to be protein damaging. Frequently, mutated genes were MEN1, DAXX, ATRX, TSC2, PI3K/Akt/mTOR and MAPK-ERK pathway-related genes. Additionally, recurrent alterations on the same genomic position, so-called hotspot mutations, were found in DAXX, PTCH2 and CYFIP2. This first ultra-deep sequencing study highlighted genetic intra-tumor heterogeneity in pNEN, by the presence of lowabundance mutations. The importance of the ATRX/DAXX pathway was confirmed by the first-ever pNEN-specific protein-damaging hotspot mutation in DAXX. In this study, both novel genes, including the pro-apoptotic CYFIP2 gene and hedgehog signaling PTCH2, and novel pathways, such as the MAPK-ERK pathway, were implicated in pNEN. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

46. Fine mapping and candidate gene screening of the deafness locus DFNA10

Author

Wayne, S., Chen, A.H., Prasad, S., Fukushima, K., Nelissen, C.M., Verhoeven, K., Van Camp, G., Tranebjaerg, L., and Smith, R.J.H.

Subjects
Genetic research -- Analysis, Human genetics -- Research, Deafness -- Genetic aspects, Presbycusis -- Genetic aspects, Biological sciences
Published
2000

47. The M34T allele variant of Connexin 26

Author

Cucci, R.A., Prasad, S., Kelley, P.M., Green, G.E., Storm, K., Willocx, S., Cohn, E.S., Van Camp, G., and Smith, R.J.H.

Subjects
Genetic research -- Analysis, Human genetics -- Research, Hearing loss -- Genetic aspects, Biological sciences
Published
2000

50. Risk of cardiac valve regurgitation with dopamine agonist use in Parkinson's disease and hyperprolactinaemia: a multi-country, nested case-control study.

Author

Trifirò G, Mokhles MM, Dieleman JP, van Soest EM, Verhamme K, Mazzaglia G, Herings R, de Luise C, Ross D, Brusselle G, Colao A, Haverkamp W, Schade R, van Camp G, Zanettini R, Sturkenboom MC, Trifirò, Gianluca, Mokhles, M Mostafa, Dieleman, Jeanne P, and van Soest, Eva M

Abstract

Background: There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson's disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower.Objective: The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson's disease or hyperprolactinaemia.Design: Nested case-control studies conducted separately in cohorts of Parkinson's disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year.Setting and Patients: Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996-2007. The Parkinson's disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists.Main Outcome Measure: Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson's disease cohort, and dopamine agonist-naïve patients in the hyperprolactinaemia cohort.Results: In the Parkinson's disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [OR(adj)] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (OR(adj) 1.20; 95% CI 0.63, 2.29). In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14 299 dopamine agonist-naïve patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (OR(adj) 0.47; 95% CI 0.20, 1.19).Conclusion: Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson's disease but not in hyperprolactinaemia patients. [ABSTRACT FROM AUTHOR]

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results