24 results on '"Panneman, Daan M."'
Search Results
2. Reduced ech-6 expression attenuates fat-induced lifespan shortening in C. elegans
- Author
-
Liu, Yasmine J., Gao, Arwen W., Smith, Reuben L., Janssens, Georges E., Panneman, Daan M., Jongejan, Aldo, van Weeghel, Michel, Vaz, Frédéric M., Silvestrini, Melissa J., Lapierre, Louis R., MacInnes, Alyson W., and Houtkooper, Riekelt H.
- Published
- 2022
- Full Text
- View/download PDF
3. Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.
- Author
-
de Bruijn, Suzanne E., Panneman, Daan M., Weisschuh, Nicole, Cadena, Elizabeth L., Boonen, Erica G. M., Holtes, Lara K., Astuti, Galuh D. N., Cremers, Frans P. M., Leijsten, Nico, Corominas, Jordi, Gilissen, Christian, Skowronska, Anna, Woodley, Jessica, Beggs, Andrew D., Toulis, Vasileios, Chen, Di, Cheetham, Michael E., Hardcastle, Alison J., McLaren, Terri L., and Lamey, Tina M.
- Subjects
RETINITIS pigmentosa ,GENETIC regulation ,GENE mapping ,RETINAL degeneration ,NUCLEOTIDE sequencing - Abstract
Introduction: Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods. The aim of this study was to accurately detect novel RP17-SVs by establishing a systematic and efficient workflow. Methods: Genetically unexplained probands diagnosed with adRP (n = 509) from an international cohort were screened using a smMIPs or genomic qPCR-based approach tailored for the RP17 locus. Suspected copy number changes were validated using high-density SNP-array genotyping, and SV breakpoint characterization was performed by mutation-specific breakpoint PCR, genome sequencing and, if required, optical genome mapping. In silico modeling of novel SVs was performed to predict the formation of neo-TADs and whether ectopic contacts between the retinal enhancers and the GDPD1 -promoter could be formed. Results: Using this workflow, potential RP17-SVs were detected in eight probands of which seven were confirmed. Two novel SVs were identified that are predicted to cause TAD rearrangement and retinal enhancer- GDPD1 contact, one from Germany (DE-SV9) and three with the same SV from the United States (US-SV10). Previously reported RP17-SVs were also identified in three Australian probands, one with UK-SV2 and two with SA-SV3. Discussion: In summary, we describe a validated multi-step pipeline for reliable and efficient RP17-SV discovery and expand the range of disease-associated SVs. Based on these data, RP17-SVs can be considered a frequent cause of adRP which warrants the inclusion of RP17-screening as a standard diagnostic test for this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes
- Author
-
Hitti-Malin, Rebekkah J., primary, Panneman, Daan M., additional, Corradi, Zelia, additional, Boonen, Erica G. M., additional, Astuti, Galuh, additional, Dhaenens, Claire-Marie, additional, Stöhr, Heidi, additional, Weber, Bernhard H. F., additional, Sharon, Dror, additional, Banin, Eyal, additional, Karali, Marianthi, additional, Banfi, Sandro, additional, Ben-Yosef, Tamar, additional, Glavač, Damjan, additional, Farrar, G. Jane, additional, Ayuso, Carmen, additional, Liskova, Petra, additional, Dudakova, Lubica, additional, Vajter, Marie, additional, Ołdak, Monika, additional, Szaflik, Jacek P., additional, Matynia, Anna, additional, Gorin, Michael B., additional, Kämpjärvi, Kati, additional, Bauwens, Miriam, additional, De Baere, Elfride, additional, Hoyng, Carel B., additional, Li, Catherina H. Z., additional, Klaver, Caroline C. W., additional, Inglehearn, Chris F., additional, Fujinami, Kaoru, additional, Rivolta, Carlo, additional, Allikmets, Rando, additional, Zernant, Jana, additional, Lee, Winston, additional, Podhajcer, Osvaldo L., additional, Fakin, Ana, additional, Sajovic, Jana, additional, AlTalbishi, Alaa, additional, Valeina, Sandra, additional, Taurina, Gita, additional, Vincent, Andrea L., additional, Roberts, Lisa, additional, Ramesar, Raj, additional, Sartor, Giovanna, additional, Luppi, Elena, additional, Downes, Susan M., additional, van den Born, L. Ingeborgh, additional, McLaren, Terri L., additional, De Roach, John N., additional, Lamey, Tina M., additional, Thompson, Jennifer A., additional, Chen, Fred K., additional, Tracewska, Anna M., additional, Kamakari, Smaragda, additional, Sallum, Juliana Maria Ferraz, additional, Bolz, Hanno J., additional, Kayserili, Hülya, additional, Roosing, Susanne, additional, and Cremers, Frans P. M., additional
- Published
- 2024
- Full Text
- View/download PDF
5. Cost‐effective smMIPs‐based sequencing to provide a genetic diagnosis for patients with retinitis pigmentosa, Leber congenital amaurosis and macular diseases
- Author
-
Panneman, Daan M., primary, Hitti‐Malin, Rebekkah J., additional, Roosing, Susanne, additional, and Cremers, Frans P. M., additional
- Published
- 2024
- Full Text
- View/download PDF
6. Elevated Plasma Complement Factors in CRB1-associated Inherited Retinal Dystrophies
- Author
-
Moekotte, Lude, primary, Boer, Joke H., additional, Hiddingh, Sanne, additional, Ligt, Aafke, additional, Nguyen, Xuan-Thanh-An, additional, Hoyng, Carel B., additional, Inglehearn, Chris F., additional, McKibbin, Martin, additional, Lamey, Tina M., additional, Thompson, Jennifer A., additional, Chen, Fred K., additional, McLaren, Terri L., additional, AlTalbishi, Alaa, additional, Panneman, Daan M., additional, Boonen, Erica G.M., additional, Banfi, Sandro, additional, Bocquet, Beatrice, additional, Meunier, Isabelle, additional, Baere, Elfride, additional, Koenekoop, Robert, additional, Oldak, Monika, additional, Rivolta, Carlo, additional, Roberts, Lisa, additional, Ramesar, Raj, additional, Strupaite-Sileikiene, Rasa, additional, Kohl, Susanne, additional, Farrar, G. Jane, additional, Vugt, Marion, additional, Setten, Jessica, additional, Roosing, Susanne, additional, Born, L. Ingeborgh, additional, Boon, Camiel J.F., additional, Genderen, Maria M., additional, and Kuiper, Jonas J.W., additional
- Published
- 2023
- Full Text
- View/download PDF
7. In Vitro Skeletal Muscle Model of PGM1 Deficiency Reveals Altered Energy Homeostasis
- Author
-
Conte, Federica, primary, Ashikov, Angel, additional, Mijdam, Rachel, additional, van de Ven, Eline G. P., additional, van Scherpenzeel, Monique, additional, Veizaj, Raisa, additional, Mahalleh-Yousefi, Seyed P., additional, Post, Merel A., additional, Huijben, Karin, additional, Panneman, Daan M., additional, Rodenburg, Richard J. T., additional, Voermans, Nicol C., additional, Garanto, Alejandro, additional, Koopman, Werner J. H., additional, Wessels, Hans J. C. T., additional, Noga, Marek J., additional, and Lefeber, Dirk J., additional
- Published
- 2023
- Full Text
- View/download PDF
8. Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- Author
-
Novartis, Foundation Fighting Blindness, Ghent University, Research Foundation - Flanders, European Commission, Panneman, Daan M., Hitti-Malin, Rebekkah J., Holtes, Lara K., Bruijn, Suzanne E. de, Reurink, Janine, Boonen, Erica G. M., Khan, Muhammad Imran, Ali, Manir, Andréasson, Sten, De Baere, Elfride, Banfi, Sandro, Bauwens, Miriam, Ben-Yosef, Tamar, Bocquet, Béatrice, De Bruyne, Marieke, Cerda, Berta de la, Coppieters, Frauke, Farinelli, Pietro, Guignard, Thomas, Inglehearn, Chris F., Karali, Marianthi, Kjellström, Ulrika, Koenekoop, Robert, Koning, Bart de, Leroy, Bart P., McKibbin, Martin, Meunier, Isabelle, Nikopoulos, Konstantinos, Nishiguchi, Koji M., Poulter, James A., Rivolta, Carlo, Rodríguez de la Rúa, Enrique, Saunders, Patrick, Simonelli, Francesca, Tatour, Yasmin, Testa, Francesco, Thiadens, Alberta A. H. J., Toomes, Carmel, Tracewska, Anna M., Tran, Hoai Viet, Ushida, Hiroaki, Vaclavik, Veronika, Verhoeven, Virginie J. M., Vorst, Maartje van de, Gilissen, Christian, Hoischen, Alexander, Cremers, Frans P. M., Roosing, Susanne, Novartis, Foundation Fighting Blindness, Ghent University, Research Foundation - Flanders, European Commission, Panneman, Daan M., Hitti-Malin, Rebekkah J., Holtes, Lara K., Bruijn, Suzanne E. de, Reurink, Janine, Boonen, Erica G. M., Khan, Muhammad Imran, Ali, Manir, Andréasson, Sten, De Baere, Elfride, Banfi, Sandro, Bauwens, Miriam, Ben-Yosef, Tamar, Bocquet, Béatrice, De Bruyne, Marieke, Cerda, Berta de la, Coppieters, Frauke, Farinelli, Pietro, Guignard, Thomas, Inglehearn, Chris F., Karali, Marianthi, Kjellström, Ulrika, Koenekoop, Robert, Koning, Bart de, Leroy, Bart P., McKibbin, Martin, Meunier, Isabelle, Nikopoulos, Konstantinos, Nishiguchi, Koji M., Poulter, James A., Rivolta, Carlo, Rodríguez de la Rúa, Enrique, Saunders, Patrick, Simonelli, Francesca, Tatour, Yasmin, Testa, Francesco, Thiadens, Alberta A. H. J., Toomes, Carmel, Tracewska, Anna M., Tran, Hoai Viet, Ushida, Hiroaki, Vaclavik, Veronika, Verhoeven, Virginie J. M., Vorst, Maartje van de, Gilissen, Christian, Hoischen, Alexander, Cremers, Frans P. M., and Roosing, Susanne
- Abstract
Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
- Published
- 2023
9. In Vitro Skeletal Muscle Model of PGM1 Deficiency Reveals Altered Energy Homeostasis
- Author
-
Conte, Federica, Ashikov, Angel, Mijdam, Rachel, van de Ven, Eline G.P., van Scherpenzeel, Monique, Veizaj, Raisa, Mahalleh-Yousefi, Seyed P., Post, Merel A., Huijben, Karin, Panneman, Daan M., Rodenburg, Richard J.T., Voermans, Nicol C., Garanto, Alejandro, Koopman, Werner J.H., Wessels, Hans J.C.T., Noga, Marek J., Lefeber, Dirk J., Conte, Federica, Ashikov, Angel, Mijdam, Rachel, van de Ven, Eline G.P., van Scherpenzeel, Monique, Veizaj, Raisa, Mahalleh-Yousefi, Seyed P., Post, Merel A., Huijben, Karin, Panneman, Daan M., Rodenburg, Richard J.T., Voermans, Nicol C., Garanto, Alejandro, Koopman, Werner J.H., Wessels, Hans J.C.T., Noga, Marek J., and Lefeber, Dirk J.
- Abstract
Phosphoglucomutase 1 (PGM1) is a key enzyme for the regulation of energy metabolism from glycogen and glycolysis, as it catalyzes the interconversion of glucose 1-phosphate and glucose 6-phosphate. PGM1 deficiency is an autosomal recessive disorder characterized by a highly heterogenous clinical spectrum, including hypoglycemia, cleft palate, liver dysfunction, growth delay, exercise intolerance, and dilated cardiomyopathy. Abnormal protein glycosylation has been observed in this disease. Oral supplementation with D-galactose efficiently restores protein glycosylation by replenishing the lacking pool of UDP-galactose, and rescues some symptoms, such as hypoglycemia, hepatopathy, and growth delay. However, D-galactose effects on skeletal muscle and heart symptoms remain unclear. In this study, we established an in vitro muscle model for PGM1 deficiency to investigate the role of PGM1 and the effect of D-galactose on nucleotide sugars and energy metabolism. Genome-editing of C2C12 myoblasts via CRISPR/Cas9 resulted in Pgm1 (mouse homologue of human PGM1, according to updated nomenclature) knockout clones, which showed impaired maturation to myotubes. No difference was found for steady-state levels of nucleotide sugars, while dynamic flux analysis based on 13C6-galactose suggested a block in the use of galactose for energy production in knockout myoblasts. Subsequent analyses revealed a lower basal respiration and mitochondrial ATP production capacity in the knockout myoblasts and myotubes, which were not restored by D-galactose. In conclusion, an in vitro mouse muscle cell model has been established to study the muscle-specific metabolic mechanisms in PGM1 deficiency, which suggested that galactose was unable to restore the reduced energy production capacity.
- Published
- 2023
10. Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- Author
-
Panneman, Daan M., Hitti-Malin, Rebekkah J., Holtes, Lara K., de Bruijn, Suzanne E., Reurink, Janine, Boonen, Erica G.M., Khan, Muhammad Imran, Ali, Manir, Andréasson, Sten, De Baere, Elfride, Banfi, Sandro, Bauwens, Miriam, Ben-Yosef, Tamar, Bocquet, Béatrice, De Bruyne, Marieke, Cerda, Berta de la, Coppieters, Frauke, Farinelli, Pietro, Guignard, Thomas, Inglehearn, Chris F., Karali, Marianthi, Kjellström, Ulrika, Koenekoop, Robert, de Koning, Bart, Leroy, Bart P., McKibbin, Martin, Meunier, Isabelle, Nikopoulos, Konstantinos, Nishiguchi, Koji M., Poulter, James A., Rivolta, Carlo, Rodríguez de la Rúa, Enrique, Saunders, Patrick, Simonelli, Francesca, Tatour, Yasmin, Testa, Francesco, Thiadens, Alberta A.H.J., Toomes, Carmel, Tracewska, Anna M., Tran, Hoai Viet, Ushida, Hiroaki, Vaclavik, Veronika, Verhoeven, Virginie J.M., van de Vorst, Maartje, Gilissen, Christian, Hoischen, Alexander, Cremers, Frans P.M., Roosing, Susanne, Panneman, Daan M., Hitti-Malin, Rebekkah J., Holtes, Lara K., de Bruijn, Suzanne E., Reurink, Janine, Boonen, Erica G.M., Khan, Muhammad Imran, Ali, Manir, Andréasson, Sten, De Baere, Elfride, Banfi, Sandro, Bauwens, Miriam, Ben-Yosef, Tamar, Bocquet, Béatrice, De Bruyne, Marieke, Cerda, Berta de la, Coppieters, Frauke, Farinelli, Pietro, Guignard, Thomas, Inglehearn, Chris F., Karali, Marianthi, Kjellström, Ulrika, Koenekoop, Robert, de Koning, Bart, Leroy, Bart P., McKibbin, Martin, Meunier, Isabelle, Nikopoulos, Konstantinos, Nishiguchi, Koji M., Poulter, James A., Rivolta, Carlo, Rodríguez de la Rúa, Enrique, Saunders, Patrick, Simonelli, Francesca, Tatour, Yasmin, Testa, Francesco, Thiadens, Alberta A.H.J., Toomes, Carmel, Tracewska, Anna M., Tran, Hoai Viet, Ushida, Hiroaki, Vaclavik, Veronika, Verhoeven, Virginie J.M., van de Vorst, Maartje, Gilissen, Christian, Hoischen, Alexander, Cremers, Frans P.M., and Roosing, Susanne
- Abstract
Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
- Published
- 2023
11. Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- Author
-
Panneman, Daan M., primary, Hitti-Malin, Rebekkah J., additional, Holtes, Lara K., additional, de Bruijn, Suzanne E., additional, Reurink, Janine, additional, Boonen, Erica G. M., additional, Khan, Muhammad Imran, additional, Ali, Manir, additional, Andréasson, Sten, additional, De Baere, Elfride, additional, Banfi, Sandro, additional, Bauwens, Miriam, additional, Ben-Yosef, Tamar, additional, Bocquet, Béatrice, additional, De Bruyne, Marieke, additional, Cerda, Berta de la, additional, Coppieters, Frauke, additional, Farinelli, Pietro, additional, Guignard, Thomas, additional, Inglehearn, Chris F., additional, Karali, Marianthi, additional, Kjellström, Ulrika, additional, Koenekoop, Robert, additional, de Koning, Bart, additional, Leroy, Bart P., additional, McKibbin, Martin, additional, Meunier, Isabelle, additional, Nikopoulos, Konstantinos, additional, Nishiguchi, Koji M., additional, Poulter, James A., additional, Rivolta, Carlo, additional, Rodríguez de la Rúa, Enrique, additional, Saunders, Patrick, additional, Simonelli, Francesca, additional, Tatour, Yasmin, additional, Testa, Francesco, additional, Thiadens, Alberta A. H. J., additional, Toomes, Carmel, additional, Tracewska, Anna M., additional, Tran, Hoai Viet, additional, Ushida, Hiroaki, additional, Vaclavik, Veronika, additional, Verhoeven, Virginie J. M., additional, van de Vorst, Maartje, additional, Gilissen, Christian, additional, Hoischen, Alexander, additional, Cremers, Frans P. M., additional, and Roosing, Susanne, additional
- Published
- 2023
- Full Text
- View/download PDF
12. Effective smMIPs-Based Sequencing of Maculopathy-Associated Genes in Stargardt Disease Cases and Allied Maculopathies from the UK
- Author
-
Mc Clinton, Benjamin, primary, Corradi, Zelia, additional, McKibbin, Martin, additional, Panneman, Daan M., additional, Roosing, Susanne, additional, Boonen, Erica G. M., additional, Ali, Manir, additional, Watson, Christopher M., additional, Steel, David H., additional, Cremers, Frans P. M., additional, Inglehearn, Chris F., additional, Hitti-Malin, Rebekkah J., additional, and Toomes, Carmel, additional
- Published
- 2023
- Full Text
- View/download PDF
13. Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- Author
-
Panneman, Daan M., primary, Hitti-Malin, Rebekkah J., additional, Holtes, Lara K., additional, de Bruijn, Suzanne E., additional, Reurink, Janine, additional, Boonen, Erica G.M., additional, Khan, Muhammad Imran, additional, Ali, Manir, additional, Andréasson, Sten, additional, De Baere, Elfride, additional, Banfi, Sandro, additional, Bauwens, Miriam, additional, Ben-Yosef, Tamar, additional, Bocquet, Béatrice, additional, De Bruyne, Marieke, additional, de la Cerda, Berta, additional, Coppieters, Frauke, additional, Farinelli, Pietro, additional, Guignard, Thomas, additional, Inglehearn, Chris F., additional, Karali, Marianthi, additional, Kjellström, Ulrika, additional, Koenekoop, Robert, additional, de Koning, Bart, additional, Leroy, Bart P., additional, McKibbin, Martin, additional, Meunier, Isabelle, additional, Nikopoulos, Konstantinos, additional, Nishiguchi, Koji M., additional, Poulter, James A., additional, Rivolta, Carlo, additional, Rodríguez de la Rúa, Enrique, additional, Saunders, Patrick, additional, Simonelli, Francesca, additional, Tatour, Yasmin, additional, Testa, Francesco, additional, Thiadens, Alberta A.H.J., additional, Toomes, Carmel, additional, Tracewska, Anna M., additional, Viet Tran, Hoai, additional, Ushida, Hiroaki, additional, Vaclavik, Veronika, additional, Verhoeven, Virginie J.M., additional, van de Vorst, Maartje, additional, Gilissen, Christian, additional, Hoischen, Alexander, additional, Cremers, Frans P.M., additional, and Roosing, Susanne, additional
- Published
- 2022
- Full Text
- View/download PDF
14. Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.
- Author
-
Yosef, Tamar Ben, Banin, Eyal, Chervinsky, Elana, Shalev, Stavit A., Leibu, Rina, Mezer, Eedy, Rotenstreich, Ygal, Goldenberg-Cohen, Nitza, Weiss, Shirel, Khan, Muhammad Imran, Panneman, Daan M., Hitti-Malin, Rebekkah J., Weiner, Chen, Roosing, Susanne, Cremers, Frans P. M., Pras, Eran, Zur, Dinah, Newman, Hadas, Deitch, Iris, and Sharon, Dror
- Published
- 2023
15. Using single molecule Molecular Inversion Probes as a cost‐effective, high‐throughput sequencing approach to target all genes and loci associated with macular diseases.
- Author
-
Hitti‐Malin, Rebekkah J., Dhaenens, Claire‐Marie, Panneman, Daan M., Corradi, Zelia, Khan, Mubeen, den Hollander, Anneke I., Farrar, G. Jane, Gilissen, Christian, Hoischen, Alexander, van de Vorst, Maartje, Bults, Femke, Boonen, Erica G. M., Saunders, Patrick, Roosing, Susanne, and Cremers, Frans P. M.
- Abstract
Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age‐related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs‐based sequencing of all MD‐associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 iMD and AMD‐associated genes and noncoding or regulatory loci, known pseudo‐exons, and the mitochondrial genome in two test cohorts that were previously screened for variants in ABCA4. Following detailed sequencing analysis of 110 probands, a diagnostic yield of 38% was observed. This established an "MD‐smMIPs panel," enabling a genotype‐first approach in a high‐throughput and cost‐effective manner, whilst achieving uniform and high coverage across targets. Further analysis will identify known and novel variants in MD‐associated genes to offer an accurate clinical diagnosis to patients. Furthermore, this will reveal new genetic associations for MD and potential genetic overlaps between iMD and AMD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
16. Soluble adenylyl cyclase regulates the cytosolic NADH/NAD+ redox state and the bioenergetic switch between glycolysis and oxidative phosphorylation
- Author
-
Chang, Jung-Chin, primary, Go, Simei, additional, Gilglioni, Eduardo H., additional, Duijst, Suzanne, additional, Panneman, Daan M., additional, Rodenburg, Richard J., additional, Li, Hang Lam, additional, Huang, Hsu-Li, additional, Levin, Lonny R., additional, Buck, Jochen, additional, Verhoeven, Arthur J., additional, and Oude Elferink, Ronald P.J., additional
- Published
- 2021
- Full Text
- View/download PDF
17. Variants in NGLY1 lead to intellectual disability, myoclonus epilepsy, sensorimotor axonal polyneuropathy and mitochondrial dysfunction
- Author
-
Cluster C, Metabole ziekten patientenzorg, Infection & Immunity, Child Health, Panneman, Daan M, Wortmann, Saskia B, Haaxma, Charlotte A, van Hasselt, Peter M, Wolf, Nicole I, Hendriks, Yvonne, Küsters, Benno, van Emst-de Vries, Sjenet, van de Westerlo, Els, Koopman, Werner J H, Wintjes, Liesbeth, van den Brandt, Frans, de Vries, Maaike, Lefeber, Dirk J, Smeitink, Jan A M, Rodenburg, Richard J, Cluster C, Metabole ziekten patientenzorg, Infection & Immunity, Child Health, Panneman, Daan M, Wortmann, Saskia B, Haaxma, Charlotte A, van Hasselt, Peter M, Wolf, Nicole I, Hendriks, Yvonne, Küsters, Benno, van Emst-de Vries, Sjenet, van de Westerlo, Els, Koopman, Werner J H, Wintjes, Liesbeth, van den Brandt, Frans, de Vries, Maaike, Lefeber, Dirk J, Smeitink, Jan A M, and Rodenburg, Richard J
- Published
- 2020
18. Variants in NGLY1 lead to intellectual disability, myoclonus epilepsy, sensorimotor axonal polyneuropathy and mitochondrial dysfunction
- Author
-
Panneman, Daan M., Wortmann, Saskia B., Haaxma, Charlotte A., van Hasselt, Peter M., Wolf, Nicole I., Hendriks, Yvonne, Küsters, Benno, van Emst-de Vries, Sjenet, van de Westerlo, Els, Koopman, Werner J.H., Wintjes, Liesbeth, van den Brandt, Frans, de Vries, Maaike, Lefeber, Dirk J., Smeitink, Jan A.M., Rodenburg, Richard J., Panneman, Daan M., Wortmann, Saskia B., Haaxma, Charlotte A., van Hasselt, Peter M., Wolf, Nicole I., Hendriks, Yvonne, Küsters, Benno, van Emst-de Vries, Sjenet, van de Westerlo, Els, Koopman, Werner J.H., Wintjes, Liesbeth, van den Brandt, Frans, de Vries, Maaike, Lefeber, Dirk J., Smeitink, Jan A.M., and Rodenburg, Richard J.
- Abstract
NGLY1 encodes the enzyme N-glycanase that is involved in the degradation of glycoproteins as part of the endoplasmatic reticulum-associated degradation pathway. Variants in this gene have been described to cause a multisystem disease characterized by neuromotor impairment, neuropathy, intellectual disability, and dysmorphic features. Here, we describe four patients with pathogenic variants in NGLY1. As the clinical features and laboratory results of the patients suggested a multisystem mitochondrial disease, a muscle biopsy had been performed. Biochemical analysis in muscle showed a strongly reduced ATP production rate in all patients, while individual OXPHOS enzyme activities varied from normal to reduced. No causative variants in any mitochondrial disease genes were found using mtDNA analysis and whole exome sequencing. In all four patients, variants in NGLY1 were identified, including two unreported variants (c.849T>G (p.(Cys283Trp)) and c.1067A>G (p.(Glu356Gly)). Western blot analysis of N-glycanase in muscle and fibroblasts showed a complete absence of N-glycanase. One patient showed a decreased basal and maximal oxygen consumption rates in fibroblasts. Mitochondrial morphofunction fibroblast analysis showed patient specific differences when compared to control cell lines. In conclusion, variants in NGLY1 affect mitochondrial energy metabolism which in turn might contribute to the clinical disease course.
- Published
- 2020
19. Reduced ech-6 Expression Attenuates Fat-induced Premature Aging in C. elegans
- Author
-
Liu, Yasmine J., primary, Gao, Arwen W., additional, Smith, Reuben L., additional, Janssens, Georges E., additional, Panneman, Daan M., additional, Jongejan, Aldo, additional, van Weeghel, Michel, additional, Vaz, Frédéric M., additional, Silvestrini, Melissa J., additional, Lapierre, Louis R., additional, MacInnes, Alyson W., additional, and Houtkooper, Riekelt H., additional
- Published
- 2020
- Full Text
- View/download PDF
20. Variants in NGLY1 lead to intellectual disability, myoclonus epilepsy, sensorimotor axonal polyneuropathy and mitochondrial dysfunction
- Author
-
Panneman, Daan M., primary, Wortmann, Saskia B., additional, Haaxma, Charlotte A., additional, Hasselt, Peter M., additional, Wolf, Nicole I., additional, Hendriks, Yvonne, additional, Küsters, Benno, additional, Emst‐de Vries, Sjenet, additional, Westerlo, Els, additional, Koopman, Werner J.H., additional, Wintjes, Liesbeth, additional, Brandt, Frans, additional, Vries, Maaike, additional, Lefeber, Dirk J., additional, Smeitink, Jan A.M., additional, and Rodenburg, Richard J., additional
- Published
- 2020
- Full Text
- View/download PDF
21. Bi-Allelic UQCRFS1 Variants Are Associated with Mitochondrial Complex III Deficiency, Cardiomyopathy, and Alopecia Totalis
- Author
-
Gusic, Mirjana, primary, Schottmann, Gudrun, additional, Feichtinger, René G., additional, Du, Chen, additional, Scholz, Caroline, additional, Wagner, Matias, additional, Mayr, Johannes A., additional, Lee, Chae-Young, additional, Yépez, Vicente A., additional, Lorenz, Norbert, additional, Morales-Gonzalez, Susanne, additional, Panneman, Daan M., additional, Rötig, Agnès, additional, Rodenburg, Richard J.T., additional, Wortmann, Saskia B., additional, Prokisch, Holger, additional, and Schuelke, Markus, additional
- Published
- 2020
- Full Text
- View/download PDF
22. Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- Author
-
Daan M. Panneman, Rebekkah J. Hitti-Malin, Lara K. Holtes, Suzanne E. de Bruijn, Janine Reurink, Erica G.M. Boonen, Muhammad Imran Khan, Manir Ali, Sten Andréasson, Elfride De Baere, Sandro Banfi, Miriam Bauwens, Tamar Ben-Yosef, Béatrice Bocquet, Marieke De Bruyne, Berta de la Cerda, Frauke Coppieters, Pietro Farinelli, Thomas Guignard, Chris F. Inglehearn, Marianthi Karali, Ulrika Kjellström, Robert Koenekoop, Bart de Koning, Bart P. Leroy, Martin McKibbin, Isabelle Meunier, Konstantinos Nikopoulos, Koji M. Nishiguchi, James A. Poulter, Carlo Rivolta, Enrique Rodríguez de la Rúa, Patrick Saunders, Francesca Simonelli, Yasmin Tatour, Francesco Testa, Alberta A.H.J. Thiadens, Carmel Toomes, Anna M. Tracewska, Hoai Viet Tran, Hiroaki Ushida, Veronika Vaclavik, Virginie J.M. Verhoeven, Maartje van de Vorst, Christian Gilissen, Alexander Hoischen, Frans P.M. Cremers, Susanne Roosing, MUMC+: DA KG Lab Informatica en BIO (9), RS: FHML non-thematic output, Panneman, Daan M., Hitti-Malin, Rebekkah J., Holtes, Lara K., de Bruijn, Suzanne E., Reurink, Janine, Boonen, Erica G. M., Khan, Muhammad Imran, Ali, Manir, Andréasson, Sten, De Baere, Elfride, Banfi, Sandro, Bauwens, Miriam, Ben-Yosef, Tamar, Bocquet, Béatrice, De Bruyne, Marieke, Cerda, Berta de la, Coppieters, Frauke, Farinelli, Pietro, Guignard, Thoma, Inglehearn, Chris F., Karali, Marianthi, Kjellström, Ulrika, Koenekoop, Robert, de Koning, Bart, Leroy, Bart P., Mckibbin, Martin, Meunier, Isabelle, Nikopoulos, Konstantino, Nishiguchi, Koji M., Poulter, James A., Rivolta, Carlo, Rodríguez de la Rúa, Enrique, Saunders, Patrick, Simonelli, Francesca, Tatour, Yasmin, Testa, Francesco, Thiadens, Alberta A. H. J., Toomes, Carmel, Tracewska, Anna M., Tran, Hoai Viet, Ushida, Hiroaki, Vaclavik, Veronika, Verhoeven, Virginie J. M., van de Vorst, Maartje, Gilissen, Christian, Hoischen, Alexander, Cremers, Frans P. M., and Roosing, Susanne
- Subjects
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,targeted gene sequencing ,MUTATIONS ,cost-effective ,inherited retinal diseases ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Biology and Life Sciences ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,Cell Biology ,VARIANTS ,RETINAL DYSTROPHY ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,All institutes and research themes of the Radboud University Medical Center ,smMIPs ,high-throughput ,Developmental Biology - Abstract
Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies.Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases.Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
- Published
- 2023
23. Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.
- Author
-
Ben Yosef T, Banin E, Chervinsky E, Shalev SA, Leibu R, Mezer E, Rotenstreich Y, Goldenberg-Cohen N, Weiss S, Khan MI, Panneman DM, Hitti-Malin RJ, Weiner C, Roosing S, Cremers FPM, Pras E, Zur D, Newman H, Deitch I, Sharon D, and Ehrenberg M
- Subjects
- Female, Humans, Male, Jews genetics, Israel epidemiology, Pedigree, Retina, Mutation genetics, DNA Mutational Analysis, ATP-Binding Cassette Transporters genetics, Retinitis Pigmentosa epidemiology, Retinitis Pigmentosa genetics, Retinal Diseases
- Abstract
Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry., Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing)., Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4 . Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4 -c.6077delT, is likely a founder mutation among the studied population., Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future., (Copyright © 2023 Molecular Vision.)
- Published
- 2023
24. Soluble adenylyl cyclase regulates the cytosolic NADH/NAD + redox state and the bioenergetic switch between glycolysis and oxidative phosphorylation.
- Author
-
Chang JC, Go S, Gilglioni EH, Duijst S, Panneman DM, Rodenburg RJ, Li HL, Huang HL, Levin LR, Buck J, Verhoeven AJ, and Oude Elferink RPJ
- Subjects
- Adenylyl Cyclases genetics, Hep G2 Cells, Humans, Mitochondria genetics, Mitochondria metabolism, NAD genetics, Oxygen Consumption, Adenylyl Cyclases metabolism, Cytosol metabolism, Glycolysis, NAD metabolism, Oxidation-Reduction, Oxidative Phosphorylation
- Abstract
The evolutionarily conserved soluble adenylyl cyclase (sAC, ADCY10) mediates cAMP signaling exclusively in intracellular compartments. Because sAC activity is sensitive to local concentrations of ATP, bicarbonate, and free Ca
2+ , sAC is potentially an important metabolic sensor. Nonetheless, little is known about how sAC regulates energy metabolism in intact cells. In this study, we demonstrated that both pharmacological and genetic suppression of sAC resulted in increased lactate secretion and decreased pyruvate secretion in multiple cell lines and primary cultures of mouse hepatocytes and cholangiocytes. The increased extracellular lactate-to-pyruvate ratio upon sAC suppression reflected an increased cytosolic free [NADH]/[NAD+ ] ratio, which was corroborated by using the NADH/NAD+ redox biosensor Peredox-mCherry. Mechanistic studies in permeabilized HepG2 cells showed that sAC inhibition specifically suppressed complex I of the mitochondrial respiratory chain. A survey of cAMP effectors revealed that only selective inhibition of exchange protein activated by cAMP 1 (Epac1), but not protein kinase A (PKA) or Epac2, suppressed complex I-dependent respiration and significantly increased the cytosolic NADH/NAD+ redox state. Analysis of the ATP production rate and the adenylate energy charge showed that inhibiting sAC reciprocally affects ATP production by glycolysis and oxidative phosphorylation while maintaining cellular energy homeostasis. In conclusion, our study shows that, via the regulation of complex I-dependent mitochondrial respiration, sAC-Epac1 signaling regulates the cytosolic NADH/NAD+ redox state, and coordinates oxidative phosphorylation and glycolysis to maintain cellular energy homeostasis. As such, sAC is effectively a bioenergetic switch between aerobic glycolysis and oxidative phosphorylation at the post-translational level., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.