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PubMed Publications| Keyword search (4,163 papers available) |  |
"Sacher M" Authored Publications:
| Title | Authors | PubMed ID | |
|---|---|---|---|
| 1 | Cross-species evaluation of TANGO2 homologs, including HRG-9 and HRG-10 in em Caenorhabditis elegans, /em challenges a proposed role in heme trafficking | Sandkuhler SE; Youngs KS; Gottipalli O; Owlett LD; Bandora MB; Naaz A; Kim E; Wang L; Wojtovich A; Gupta V; Sacher M; Mackenzie SJ; | 41504601 BIOLOGY |
| 2 | SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis | Bögershausen N; Cavdarli B; Nagai T; Milev MP; Wolff A; Mehranfar M; Schmidt J; Choudhary D; Gutiérrez-Gutiérrez Ó; Cyganek L; Saint-Dic D; Zibat A; Köhrer K; Wollenweber TE; Wieczorek D; Altmüller J; Borodina T; Kaçar D; Haliloglu G; Li Y; Thiel C; Sacher M; Knapik EW; Yigit G; Wollnik B; | 40131364 BIOLOGY |
| 3 | Imaging flow cytometry-based cellular screening elucidates pathophysiology in individuals with Variants of Uncertain Significance | Muffels IJJ; Waterham HR; D' Alessandro G; Zagnoli-Vieira G; Sacher M; Lefeber DJ; Van der Vinne C; Roifman CM; Gassen KLI; Rehmann H; Van Haaften-Visser DY; Nieuwenhuis ESS; Jackson SP; Fuchs SA; Wijk F; van Hasselt P; | 39920830 BIOLOGY |
| 4 | A Humanized Yeast Model for Studying TRAPP Complex Mutations; Proof-of-Concept Using Variants from an Individual with a TRAPPC1-Associated Neurodevelopmental Syndrome | Zykaj E; Abboud C; Asadi P; Warsame S; Almousa H; Milev MP; Greco BM; López-Sánchez M; Bratkovic D; Kachroo AH; Pérez-Jurado LA; Sacher M; | 39273027 BIOLOGY |
| 5 | TANGO2 deficiency disease is predominantly caused by a lipid imbalance | Sacher M; DeLoriea J; Mehranfar M; Casey C; Naaz A; Gamberi C; | 38836374 BIOLOGY |
| 6 | Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients | Miyake CY; Lay EJ; Soler-Alfonso C; Glinton KE; Houck KM; Tosur M; Moran NE; Stephens SB; Scaglia F; Howard TS; Kim JJ; Pham TD; Valdes SO; Li N; Murali CN; Zhang L; Kava M; Yim D; Beach C; Webster G; Liberman L; Janson CM; Kannankeril PJ; Baxter S; Singer-Berk M; Wood J; Mackenzie SJ; Sacher M; Ghaloul-Gonzalez L; Pedroza C; Morris SA; Ehsan SA; Azamian MS; Lalani SR; | 36473599 BIOLOGY |
| 7 | Dynamic regulation of inter-organelle communication by ubiquitylation controls skeletal muscle development and disease onset | Mansur A; Joseph R; Kim ES; Jean-Beltran PM; Udeshi ND; Pearce C; Jiang H; Iwase R; Milev MP; Almousa HA; McNamara E; Widrick J; Perez C; Ravenscroft G; Sacher M; Cole PA; Carr SA; Gupta VA; | 37432316 BIOLOGY |
| 8 | Vitamin B5, a Coenzyme A precursor, rescues TANGO2 deficiency disease-associated defects in Drosophila and human cells | Asadi P; Milev MP; Saint-Dic D; Gamberi C; Sacher M; | 36502486 BIOLOGY |
| 9 | Biallelic variants in TRAPPC10 cause a microcephalic TRAPPopathy disorder in humans and mice | Rawlins LE; Almousa H; Khan S; Collins SC; Milev MP; Leslie J; Saint-Dic D; Khan V; Hincapie AM; Day JO; McGavin L; Rowley C; Harlalka GV; Vancollie VE; Ahmad W; Lelliott CJ; Gul A; Yalcin B; Crosby AH; Sacher M; Baple EL; | 35298461 BIOLOGY |
| 10 | TRAPPC11-related muscular dystrophy with hypoglycosylation of alpha-dystroglycan in skeletal muscle and brain | Munot P; McCrea N; Torelli S; Manzur A; Sewry C; Chambers D; Feng L; Ala P; Zaharieva I; Ragge N; Roper H; Marton T; Cox P; Milev MP; Liang WC; Maruyama S; Nishino I; Sacher M; Phadke R; Muntoni F; | 34648194 BIOLOGY |
| 11 | Publisher Correction: Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein. | Milev MP; Stanga D; Schänzer A; Nascimento A; Saint-Dic D; Ortez C; Natera-de Benito D; Barrios DG; Colomer J; Badosa C; Jou C; Gallano P; Gonzalez-Quereda L; Töpf A; Johnson K; Straub V; Hahn A; Sacher M; Jimenez-Mallebrera C; | 33173071 BIOLOGY |
| 12 | The phenotype associated with variants in TANGO2 may be explained by a dual role of the protein in ER-to-Golgi transport and at the mitochondria. | Milev MP, Saint-Dic D, Zardoui K, Klopstock T, Law C, Distelmaier F, Sacher M | 32909282 BIOLOGY |
| 13 | A novel homozygous variant in TRAPPC2L results in a neurodevelopmental disorder and disrupts TRAPP complex function. | Al-Deri N, Okur V, Ahimaz P, Milev M, Valivullah Z, Hagen J, Sheng Y, Chung W, Sacher M, Ganapathi M | 32843486 BIOLOGY |
| 14 | TRAPPing a neurological disorder: from yeast to humans. | Lipatova Z, Van Bergen N, Stanga D, Sacher M, Christodoulou J, Segev N | 32116085 BIOLOGY |
| 15 | Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability. | Van Bergen NJ, Guo Y, Al-Deri N, Lipatova Z, Stanga D, Zhao S, Murtazina R, Gyurkovska V, Pehlivan D, Mitani T, Gezdirici A, Antony J, Collins F, Willis MJH, Coban Akdemir ZH, Liu P, Punetha J, Hunter JV, Jhangiani SN, Fatih JM, Rosenfeld JA, Posey JE, Gibbs RA, Karaca E, Massey S, Ranasinghe TG, Sleiman P, Troedson C, Lupski JR, Sacher M, Segev N, Hakonarson H, Christodoulou J | 31794024 BIOLOGY |
| 16 | Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein. | Milev MP, Stanga D, Schänzer A, Nascimento A, Saint-Dic D, Ortez C, Benito DN, Barrios DG, Colomer J, Badosa C, Jou C, Gallano P, Gonzalez-Quereda L, Töpf A, Johnson K, Straub V, Hahn A, Sacher M, Jimenez-Mallebrera C | 31575891 BIOLOGY |
| 17 | Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction. | Milev MP, Grout ME, Saint-Dic D, Cheng YH, Glass IA, Hale CJ, Hanna DS, Dorschner MO, Prematilake K, Shaag A, Elpeleg O, Sacher M, Doherty D, Edvardson S | 28777934 BIOLOGY |
| 18 | TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment. | Milev MP, Hasaj B, Saint-Dic D, Snounou S, Zhao Q, Sacher M | 25918224 BIOLOGY |
| 19 | TRAPPC11 and GOSR2 mutations associate with hypoglycosylation of α-dystroglycan and muscular dystrophy. | Larson AA, Baker PR, Milev MP, Press CA, Sokol RJ, Cox MO, Lekostaj JK, Stence AA, Bossler AD, Mueller JM, Prematilake K, Tadjo TF, Williams CA, Sacher M, Moore SA | 29855340 BIOLOGY |
| 20 | Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts. | Milev MP, Graziano C, Karall D, Kuper WFE, Al-Deri N, Cordelli DM, Haack TB, Danhauser K, Iuso A, Palombo F, Pippucci T, Prokisch H, Saint-Dic D, Seri M, Stanga D, Cenacchi G, van Gassen KLI, Zschocke J, Fauth C, Mayr JA, Sacher M, van Hasselt PM | 30120216 BIOLOGY |
| 21 | TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)-associated proteins. | Sacher M, Shahrzad N, Kamel H, Milev MP | 30152084 BIOLOGY |
| 22 | TRAPPC11 functions in autophagy by recruiting ATG2B-WIPI4/WDR45 to preautophagosomal membranes. | Stanga D, Zhao Q, Milev MP, Saint-Dic D, Jimenez-Mallebrera C, Sacher M | 30843302 CONCORDIA |
| Title: | Imaging flow cytometry-based cellular screening elucidates pathophysiology in individuals with Variants of Uncertain Significance | ||||
| Authors: | Muffels IJJ, Waterham HR, D', Alessandro G, Zagnoli-Vieira G, Sacher M, Lefeber DJ, Van der Vinne C, Roifman CM, Gassen KLI, Rehmann H, Van Haaften-Visser DY, Nieuwenhuis ESS, Jackson SP, Fuchs SA, Wijk F, van Hasselt P | ||||
| Link: | https://pubmed.ncbi.nlm.nih.gov/39920830/ | ||||
| DOI: | 10.1186/s13073-025-01433-9 | ||||
| Publication: | Genome medicine | ||||
| Keywords: | DNA damage repair defect; Functional genomics; Genetic diseases; High-throughput screening; Imaging flow cytometry; Metabolic disorders; Precision genomic diagnostics; Variant of uncertain significance; | ||||
| PMID: | 39920830 | Category: | Date Added: | 2025-02-08 | |
| Dept Affiliation: |
BIOLOGY
1 Department of Metabolic Diseases, Division Pediatrics, Wilhelmina Children's Hospital University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. i.j.j.muffels-2@umcutrecht.nl. 2 United For Metabolic Diseases (UMD), Amsterdam, the Netherlands. 3 Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases, Amsterdam UMC - AMC, Amsterdam, the Netherlands. 4 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. 5 The Gurdon Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK. 6 Department of Biology, Concordia University, Montreal, QC, Canada. 7 Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada. 8 Translational Metabolic Laboratory, Department of Neurology, Department of Human Genetics, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. 9 Department of Metabolic Diseases, Division Pediatrics, Wilhelmina Children's Hospital University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. 10 The Hospital for Sick Children and Research Institute, The University of Toronto, Toronto, Canada. 11 Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands. 12 Department of Energy and Biotechnology, Flensburg University of Applied Sciences, Flensburg, Germany. 13 Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands. 14 Center for Rare Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands. 15 Center for Translational Immunology (CTI), University Medical Center Utrecht (UMC), Utrecht University (UU), Utrecht, The Netherlands. 16 Department of Metabolic Diseases, Division Pediatrics, Wilhelmina Children's Hospital University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. p.vanhasselt@umcutrecht.nl. |
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Description: |
Background: Deciphering variants of uncertain significance (VUS) represents a major diagnostic challenge, partially due to the lack of easy-to-use and versatile cellular readouts that aid the interpretation of pathogenicity and pathophysiology. To address this challenge, we propose a high-throughput screening of cellular functionality through an imaging flow cytometry (IFC)-based platform. Methods: Six assays to evaluate autophagic-, lysosomal-, Golgi- health, mitochondrial function, ER stress, and NF-?ß activity were developed in fibroblasts. Assay sensitivity was verified with compounds (N = 5) and positive control patients (N = 6). Eight healthy controls and 20 individuals with VUS were screened. Results: All molecular compounds and positive controls showed significant changes on their cognate assays, confirming assay sensitivity. Simultaneous screening of positive control patients on all six assays revealed distinct phenotypic profiles. In addition, individuals with VUS(es) in well-known disease genes showed distinct - but similar-phenotypic profiles compared to patients with pathogenic variants in the same gene.. For all individuals with VUSes in Genes of Uncertain Significance (GUS), we found one or more of six assays were significantly altered. Broadening the screening to an untargeted approach led to the identification of two clusters that allowed for the recognition of altered cell cycle dynamics and DNA damage repair defects. Experimental follow-up of the 'DNA damage repair defect cluster' led to the discovery of highly specific defects in top2cc release from double-strand DNA breaks in one of these individuals, harboring a VUS in the RAD54L2 gene. Conclusions: Our high-throughput IFC-based platform simplifies the process of identifying VUS pathogenicity through six assays and allows for the recognition of useful pathophysiological markers that structure follow-up experiments, thereby representing a novel valuable tool for precise functional diagnostics in genomics. |
