Search

Your search keyword '"Auber, Bernd"' showing total 338 results
Start Over Author "Auber, Bernd"
338 results on '"Auber, Bernd"'

4. Benchmarking whole exome sequencing in the German network for personalized medicine

Author

Menzel, Michael, Martis-Thiele, Mihaela, Goldschmid, Hannah, Ott, Alexander, Romanovsky, Eva, Siemanowski-Hrach, Janna, Seillier, Lancelot, Brüchle, Nadina Ortiz, Maurer, Angela, Lehmann, Kjong-Van, Begemann, Matthias, Elbracht, Miriam, Meyer, Robert, Dintner, Sebastian, Claus, Rainer, Meier-Kolthoff, Jan P., Blanc, Eric, Möbs, Markus, Joosten, Maria, Benary, Manuela, Basitta, Patrick, Hölscher, Florian, Tischler, Verena, Groß, Thomas, Kutz, Oliver, Prause, Rebecca, William, Doreen, Horny, Kai, Goering, Wolfgang, Sivalingam, Sugirthan, Borkhardt, Arndt, Blank, Cornelia, Junk, Stefanie V., Yasin, Layal, Moskalev, Evgeny A., Carta, Maria Giulia, Ferrazzi, Fulvia, Tögel, Lars, Wolter, Steffen, Adam, Eugen, Matysiak, Uta, Rosenthal, Tessa, Dönitz, Jürgen, Lehmann, Ulrich, Schmidt, Gunnar, Bartels, Stephan, Hofmann, Winfried, Hirsch, Steffen, Dikow, Nicola, Göbel, Kirsten, Banan, Rouzbeh, Hamelmann, Stefan, Fink, Annette, Ball, Markus, Neumann, Olaf, Rehker, Jan, Kloth, Michael, Murtagh, Justin, Hartmann, Nils, Jurmeister, Phillip, Mock, Andreas, Kumbrink, Jörg, Jung, Andreas, Mayr, Eva-Maria, Jacob, Anne, Trautmann, Marcel, Kirmse, Santina, Falkenberg, Kim, Ruckert, Christian, Hirsch, Daniela, Immel, Alexander, Dietmaier, Wolfgang, Haack, Tobias, Marienfeld, Ralf, Fürstberger, Axel, Niewöhner, Jakob, Gerstenmaier, Uwe, Eberhardt, Timo, Greif, Philipp A., Appenzeller, Silke, Maurus, Katja, Doll, Julia, Jelting, Yvonne, Jonigk, Danny, Märkl, Bruno, Beule, Dieter, Horst, David, Wulf, Anna-Lena, Aust, Daniela, Werner, Martin, Reuter-Jessen, Kirsten, Ströbel, Philipp, Auber, Bernd, Sahm, Felix, Merkelbach-Bruse, Sabine, Siebolts, Udo, Roth, Wilfried, Lassmann, Silke, Klauschen, Frederick, Gaisa, Nadine T., Weichert, Wilko, Evert, Matthias, Armeanu-Ebinger, Sorin, Ossowski, Stephan, Schroeder, Christopher, Schaaf, Christian P., Malek, Nisar, Schirmacher, Peter, Kazdal, Daniel, Pfarr, Nicole, Budczies, Jan, and Stenzinger, Albrecht

Published
2024
Full Text
View/download PDF

8. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Author

Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel R, Allen, Jamie, Kar, Siddhartha, Pooley, Karen A, Dennis, Joe, Michailidou, Kyriaki, Turman, Constance, Soucy, Penny, Lemaçon, Audrey, Lush, Michael, Tyrer, Jonathan P, Ghoussaini, Maya, Moradi Marjaneh, Mahdi, Jiang, Xia, Agata, Simona, Aittomäki, Kristiina, Alonso, M Rosario, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Auber, Bernd, Auer, Paul L, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Amie M, Blomqvist, Carl, Blot, William, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Borg, Ake, Bosse, Kristin, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brock, Ian W, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Camp, Nicola J, Campbell, Ian, Canzian, Federico, Carroll, Jason S, Carter, Brian D, Castelao, Jose E, Chiquette, Jocelyne, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, Collée, J Margriet, Cornelissen, Sten, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian S, Domchek, Susan M, Dörk, Thilo, Dos-Santos-Silva, Isabel, Droit, Arnaud, Dubois, Stéphane, Dumont, Martine, Duran, Mercedes, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana M, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Fletcher, Olivia, Floris, Giuseppe, and Flyger, Henrik

Subjects
GEMO Study Collaborators, EMBRACE Collaborators, KConFab Investigators, HEBON Investigators, ABCTB Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Bayes Theorem, Risk Factors, Chromosome Mapping, Regulatory Sequences, Nucleic Acid, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Female, Genome-Wide Association Study, Biomarkers, Tumor, Genetic Testing, Prevention, Genetics, Cancer, Breast Cancer, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.

Published
2020

10. The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Author

Figlioli, Gisella, Bogliolo, Massimo, Catucci, Irene, Caleca, Laura, Lasheras, Sandra Viz, Pujol, Roser, Kiiski, Johanna I, Muranen, Taru A, Barnes, Daniel R, Dennis, Joe, Michailidou, Kyriaki, Bolla, Manjeet K, Leslie, Goska, Aalfs, Cora M, Adank, Muriel A, Adlard, Julian, Agata, Simona, Cadoo, Karen, Agnarsson, Bjarni A, Ahearn, Thomas, Aittomäki, Kristiina, Ambrosone, Christine B, Andrews, Lesley, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Auber, Bernd, Auvinen, Päivi, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Beane Freeman, Laura E, Beauparlant, Charles Joly, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Berger, Raanan, Bermisheva, Marina, Blanco, Amie M, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Anders, Bojesen, Stig E, Bonanni, Bernardo, Borg, Ake, Brady, Angela F, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Caldés, Trinidad, Caliebe, Almuth, Caligo, Maria A, Campa, Daniele, Campbell, Ian G, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Claes, Kathleen BM, Clarke, Christine L, Collavoli, Anita, Conner, Thomas A, Cox, David G, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian S, Ditsch, Nina, Domchek, Susan M, Dorfling, Cecilia M, dos-Santos-Silva, Isabel, Durda, Katarzyna, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Foulkes, William D, Friebel, Tara M, Friedman, Eitan, Gabrielson, Marike, Gaddam, Pragna, and Gago-Dominguez, Manuela

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Oncology and Carcinogenesis, Clinical Research, Genetics, Breast Cancer, Cancer, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, ABCTB Investigators, GEMO Study Collaborators, KConFab, Cancer genetics, Clinical sciences, Oncology and carcinogenesis, Epidemiology
Abstract

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.

Published
2019

13. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Author

Milne, Roger L, Kuchenbaecker, Karoline B, Michailidou, Kyriaki, Beesley, Jonathan, Kar, Siddhartha, Lindström, Sara, Hui, Shirley, Lemaçon, Audrey, Soucy, Penny, Dennis, Joe, Jiang, Xia, Rostamianfar, Asha, Finucane, Hilary, Bolla, Manjeet K, McGuffog, Lesley, Wang, Qin, Aalfs, Cora M, Adams, Marcia, Adlard, Julian, Agata, Simona, Ahmed, Shahana, Ahsan, Habibul, Aittomäki, Kristiina, Al-Ejeh, Fares, Allen, Jamie, Ambrosone, Christine B, Amos, Christopher I, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J, Auber, Bernd, Auer, Paul L, Ausems, Margreet GEM, Azzollini, Jacopo, Bacot, François, Balmaña, Judith, Barile, Monica, Barjhoux, Laure, Barkardottir, Rosa B, Barrdahl, Myrto, Barnes, Daniel, Barrowdale, Daniel, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Bignon, Yves-Jean, Blazer, Kathleen R, Blok, Marinus J, Blomqvist, Carl, Blot, William, Bobolis, Kristie, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Anders, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Bozsik, Aniko, Bradbury, Angela R, Brand, Judith S, Brauch, Hiltrud, Brenner, Hermann, Bressac-de Paillerets, Brigitte, Brewer, Carole, Brinton, Louise, Broberg, Per, Brooks-Wilson, Angela, Brunet, Joan, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byun, Jinyoung, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canzian, Federico, Caron, Olivier, Carracedo, Angel, Carter, Brian D, Castelao, J Esteban, Castera, Laurent, Caux-Moncoutier, Virginie, Chan, Salina B, Chang-Claude, Jenny, Chanock, Stephen J, Chen, Xiaoqing, Cheng, Ting-Yuan David, Chiquette, Jocelyne, Christiansen, Hans, Claes, Kathleen BM, Clarke, Christine L, Conner, Thomas, Conroy, Don M, and Cook, Jackie

Subjects
Biological Sciences, Genetics, Cancer, Human Genome, Prevention, Breast Cancer, Aging, Estrogen, 2.1 Biological and endogenous factors, Aetiology, BRCA1 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heterozygote, Humans, Mutation, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors, White People, ABCTB Investigators, EMBRACE, GEMO Study Collaborators, HEBON, kConFab/AOCS Investigators, NBSC Collaborators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

Published
2017

15. Increased Cancer Prevalence in Peripartum Cardiomyopathy

Author

Pfeffer, Tobias J., Schlothauer, Stella, Pietzsch, Stefan, Schaufelberger, Maria, Auber, Bernd, Ricke-Hoch, Melanie, List, Manuel, Berliner, Dominik, Abou Moulig, Valeska, König, Tobias, Arany, Zolt, Sliwa, Karen, Bauersachs, Johann, and Hilfiker-Kleiner, Denise

Published
2019
Full Text
View/download PDF

16. Bi-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis

Author

Ganapathi, Mythily, Argyriou, Loukas, Martínez-Azorín, Francisco, Morlot, Susanne, Yigit, Gökhan, Lee, Teresa M., Auber, Bernd, von Gise, Alexander, Petrey, Donald S., Thiele, Holger, Cyganek, Lukas, Sabater-Molina, María, Ahimaz, Priyanka, Cabezas-Herrera, Juan, Sorlí-García, Moisés, Zibat, Arne, Siegelin, Markus D., Burfeind, Peter, Buchovecky, Christie M., Hasenfuss, Gerd, Honig, Barry, Li, Yun, Iglesias, Alejandro D., and Wollnik, Bernd

Published
2020
Full Text
View/download PDF

17. Ciliary Ultrastructure Assessed by Transmission Electron Microscopy in Adults with Bronchiectasis and Suspected Primary Ciliary Dyskinesia but Inconclusive Genotype

Author

Staar, Ben O., primary, Hegermann, Jan, additional, Auber, Bernd, additional, Ewen, Raphael, additional, von Hardenberg, Sandra, additional, Olmer, Ruth, additional, Pink, Isabell, additional, Rademacher, Jessica, additional, Wetzke, Martin, additional, and Ringshausen, Felix C., additional

Published
2023
Full Text
View/download PDF

21. Congenital deficiency reveals critical role of ISG15 in skin homeostasis

Author

Malik, Muhammad Nasir Hayat, Waqas, Syed Fakhar-ul-Hassnain, Zeitvogel, Jana, Cheng, Jingyuan, Geffers, Robert, Gouda, Zeinab Abu-Elbaha, Elsaman, Ahmed Mahrous, Radwan, Ahmed R., Schefzyk, Matthias, Braubach, Peter, Auber, Bernd, Olmer, Ruth, Musken, Mathias, Roesner, Lennart M., Gerold, Gisa, Schuchardt, Sven, Merkert, Sylvia, Martin, Ulrich, Meissner, Felix, Werfel, Thomas, and Pessler, Frank

Subjects
Interferon -- Health aspects -- Genetic aspects -- Case studies, Genetic disorders -- Complications and side effects -- Case studies -- Diagnosis, Immunity -- Genetic aspects -- Health aspects -- Case studies, Skin -- Ulcers, Pediatric research, Health care industry
Abstract

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized [ISG15.sup.-/-] dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. [ISG15.sup.-/-] fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in [ISG15.sup.-/-] fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an [ISG15.sup.-/-] 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-[beta]1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets., Introduction Monogenic type I interferonopathies are a heterogeneous group of autoinflammatory and autoimmune disorders characterized by persistently elevated levels of type I interferons (IFN-I) (1-3). The underlying molecular mechanisms are [...]

Published
2022
Full Text
View/download PDF

22. Variants in FGF10 cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children

Author

Schütz, Katharina, primary, Schmidt, Axel, additional, Schwerk, Nicolaus, additional, Renz, Diane Miriam, additional, Gerard, Benedicte, additional, Schaefer, Elise, additional, Antal, Maria Cristina, additional, Peters, Sophia, additional, Griese, Matthias, additional, Rapp, Christina K., additional, Engels, Hartmut, additional, Cremer, Kirsten, additional, Bergmann, Anke Katharina, additional, Schmidt, Gunnar, additional, Auber, Bernd, additional, Kamp, Jan C., additional, Laenger, Florian, additional, and von Hardenberg, Sandra, additional

Published
2023
Full Text
View/download PDF

25. Variants in FGF10 cause isolated neonatal lung developmental disorder

Author

Schuetz, Katharina, primary, Schmidt, Axel, additional, Schwerk, Nicolaus, additional, Renz, Diane, additional, Gerard, Benedicte, additional, Schaefer, Elise, additional, Antal, Maria Cristina, additional, Peters, Sophia, additional, Griese, Matthias, additional, Rapp, Christina Katharina, additional, Engels, Hartmut, additional, Cremer, Kirsten, additional, Bergmann, Anke Katharina, additional, Schmidt, Gunnar, additional, Auber, Bernd, additional, Kamp, Jan C., additional, Laenger, Florian, additional, and Hardenberg, Sandra von, additional

Published
2023
Full Text
View/download PDF

28. Creation of a structured molecular genomics report for Germany as a local adaption of HL7’s Genomic Reporting Implementation Guide

Author

Stellmach, Caroline, primary, Sass, Julian, additional, Auber, Bernd, additional, Boeker, Martin, additional, Wienker, Thomas, additional, Heidel, Andrew J, additional, Benary, Manuela, additional, Schumacher, Simon, additional, Ossowski, Stephan, additional, Klauschen, Frederick, additional, Möller, Yvonne, additional, Schmutzler, Rita, additional, Ustjanzew, Arsenij, additional, Werner, Patrick, additional, Tomczak, Aurelie, additional, Hölter, Thimo, additional, and Thun, Sylvia, additional

Published
2023
Full Text
View/download PDF

31. Systematic genetic analysis of pediatric patients with autoinflammatory diseases

Author

Poker, Yvonne, Hardenberg, Sandra von, Hofmann, Winfried, Tang, Ming, Baumann, Ulrich, Schwerk, Nicolaus, Wetzke, Martin, Lindenthal, Viola, Auber, Bernd, Schlegelberger, Brigitte, Ott, Hagen, von Bismarck, Philipp, Viemann, Dorothee, Dressler, Frank, Klemann, Christian, Bergmann, Anke Katharina, Poker, Yvonne, Hardenberg, Sandra von, Hofmann, Winfried, Tang, Ming, Baumann, Ulrich, Schwerk, Nicolaus, Wetzke, Martin, Lindenthal, Viola, Auber, Bernd, Schlegelberger, Brigitte, Ott, Hagen, von Bismarck, Philipp, Viemann, Dorothee, Dressler, Frank, Klemann, Christian, and Bergmann, Anke Katharina

Abstract

Monogenic autoinflammatory diseases (AID) encompass a growing group of inborn errors of the innate immune system causing unprovoked or exaggerated systemic inflammation. Diagnosis of monogenic AID requires an accurate description of the patients’ phenotype, and the identification of highly penetrant genetic variants in single genes is pivotal. We performed whole exome sequencing (WES) of 125 pediatric patients with suspected monogenic AID in a routine genetic diagnostic setting. Datasets were analyzed in a step-wise approach to identify the most feasible diagnostic strategy. First, we analyzed a virtual gene panel including 13 genes associated with known AID and, if no genetic diagnosis was established, we then analyzed a virtual panel including 542 genes published by the International Union of Immunological Societies associated including all known inborn error of immunity (IEI). Subsequently, WES data was analyzed without pre-filtering for known AID/IEI genes. Analyzing 13 genes yielded a definite diagnosis in 16.0% (n = 20). The diagnostic yield was increased by analyzing 542 genes to 20.8% (n = 26). Importantly, expanding the analysis to WES data did not increase the diagnostic yield in our cohort, neither in single WES analysis, nor in trio-WES analysis. The study highlights that the cost- and time-saving analysis of virtual gene panels is sufficient to rapidly confirm the differential diagnosis in pediatric patients with AID. WES data or trio-WES data analysis as a first-tier diagnostic analysis in patients with suspected monogenic AID is of limited benefit.

Published
2023

32. Investigating the effects of additional truncating variants in DNA-repair genes on breast cancer risk in BRCA1-positive women

Author

Sepahi, Ilnaz, Faust, Ulrike, Sturm, Marc, Bosse, Kristin, Kehrer, Martin, Heinrich, Tilman, Grundman-Hauser, Kathrin, Bauer, Peter, Ossowski, Stephan, Susak, Hana, Varon, Raymonda, Schröck, Evelin, Niederacher, Dieter, Auber, Bernd, Sutter, Christian, Arnold, Norbert, Hahnen, Eric, Dworniczak, Bernd, Wang-Gorke, Shan, Gehrig, Andrea, Weber, Bernhard H. F., Engel, Christoph, Lemke, Johannes R., Hartkopf, Andreas, Nguyen, Huu Phuc, Riess, Olaf, and Schroeder, Christopher

Published
2019
Full Text
View/download PDF

33. Systematic genetic analysis of pediatric patients with autoinflammatory diseases

Author

Poker, Yvonne, primary, von Hardenberg, Sandra, additional, Hofmann, Winfried, additional, Tang, Ming, additional, Baumann, Ulrich, additional, Schwerk, Nicolaus, additional, Wetzke, Martin, additional, Lindenthal, Viola, additional, Auber, Bernd, additional, Schlegelberger, Brigitte, additional, Ott, Hagen, additional, von Bismarck, Philipp, additional, Viemann, Dorothee, additional, Dressler, Frank, additional, Klemann, Christian, additional, and Bergmann, Anke Katharina, additional

Published
2023
Full Text
View/download PDF

35. Phenotypic spectrum in recessive STING-associated vasculopathy with onset in infancy: Four novel cases and analysis of previously reported cases

Author

Wan, Rensheng, primary, Fänder, Johannes, additional, Zakaraia, Ia, additional, Lee-Kirsch, Min Ae, additional, Wolf, Christine, additional, Lucas, Nadja, additional, Olfe, Lisa Isabel, additional, Hendrich, Corinna, additional, Jonigk, Danny, additional, Holzinger, Dirk, additional, Steindor, Mathis, additional, Schmidt, Gunnar, additional, Davenport, Claudia, additional, Klemann, Christian, additional, Schwerk, Nicolaus, additional, Griese, Matthias, additional, Schlegelberger, Brigitte, additional, Stehling, Florian, additional, Happle, Christine, additional, Auber, Bernd, additional, Steinemann, Doris, additional, Wetzke, Martin, additional, and von Hardenberg, Sandra, additional

Published
2022
Full Text
View/download PDF

37. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R, Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E, Borg, Åke, Bozsik, Aniko, Brady, Angela F, Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen BM, GEMO Study Collaborators, EMBRACE Collaborators, Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesús, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas VO, Hanson, Helen, Hentschel, Julia, Horvath, Judit, KConFab Investigators, HEBON Investigators, Izatt, Louise, Izquierdo, Angel, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M, Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A, Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernández, Adria, Mai, Phuong L, Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N, Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N, Morrison, Patrick J, Muranen, Taru A, Murray, Alex, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nguyen-Dumont, Tu, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I, Palli, Domenico, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H, Pinto, Pedro, Porteous, Mary E, Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T, Rønlund, Karina, Rump, Andreas, Sánchez de Abajo, Ana María, Shah, Payal D, Sharif, Saba, Side, Lucy E, Singer, Christian F, Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teulé, Alex, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tommasi, Stefania, Toss, Angela, Trainer, Alison H, Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J, Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J, Schmutzler, Rita K, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Antoniou, Antonis C, Ottini, Laura, Consortium of Investigators of Modifiers of BRCA1 and BRCA2, Barnes, Daniel R [0000-0002-3781-7570], Silvestri, Valentina [0000-0003-0712-9379], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Yang, Xin [0000-0003-0037-3790], Adlard, Julian [0000-0002-1693-0435], Agnarsson, Bjarni A [0000-0001-7721-9965], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arnold, Norbert [0000-0003-4523-8808], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Barkardottir, Rosa B [0000-0003-0629-2772], Barrowdale, Daniel [0000-0003-1661-3939], Benitez, Javier [0000-0002-0923-7202], Boonen, Susanne E [0000-0002-7824-2080], Bozsik, Aniko [0000-0001-5410-9173], Brennan, Paul [0000-0003-1128-6254], Brunet, Joan [0000-0003-1945-3512], Bucalo, Agostino [0000-0003-3475-1067], Caligo, Maria A [0000-0003-0589-1829], Campbell, Ian [0000-0002-7773-4155], Cassingham, Hayley [0000-0001-9922-2321], Cini, Giulia [0000-0002-8696-8922], Claes, Kathleen BM [0000-0003-0841-7372], Coppa, Anna [0000-0001-9758-5444], Cortesi, Laura [0000-0001-8950-8561], Darder, Esther [0000-0002-7764-1397], de la Hoya, Miguel [0000-0002-8113-1410], de Putter, Robin [0000-0001-9410-8941], Del Valle, Jesús [0000-0003-3607-7045], Domchek, Susan M [0000-0002-5914-7272], Donaldson, Alan [0000-0001-9193-4172], Eason, Jacqueline [0000-0002-8711-8671], Engel, Christoph [0000-0002-7247-282X], Fostira, Florentia [0000-0003-2751-2332], Frone, Megan [0000-0001-8273-8866], Glendon, Gord [0000-0001-8630-6673], Godwin, Andrew K [0000-0002-3987-9580], Greene, Mark H [0000-0003-1852-9239], Hahnen, Eric [0000-0003-2448-7872], Hanson, Helen [0000-0002-3303-8713], Izatt, Louise [0000-0003-1258-4843], Izquierdo, Angel [0000-0003-2004-3246], James, Paul A [0000-0002-4361-4657], John, Esther M [0000-0003-3259-8003], Kroeldrup, Lone [0000-0003-3623-6536], Kruse, Torben A [0000-0002-2460-6483], Lazaro, Conxi [0000-0002-7198-5906], Lesueur, Fabienne [0000-0001-7404-4549], Matrai, Zoltan [0000-0001-8160-7100], Montagna, Marco [0000-0002-4929-2150], Monteiro, Alvaro N [0000-0002-8448-4801], Morrison, Patrick J [0000-0002-2823-1762], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Neuhausen, Susan L [0000-0001-5053-0390], Nevanlinna, Heli [0000-0002-0916-2976], Nguyen-Dumont, Tu [0000-0002-6217-0182], Niederacher, Dieter [0000-0001-6231-9226], Palli, Domenico [0000-0002-5558-2437], Parsons, Michael T [0000-0003-3242-8477], Perez-Segura, Pedro [0000-0001-5049-7199], Peterlongo, Paolo [0000-0001-6951-6855], Pinto, Pedro [0000-0001-6289-5792], Pottinger, Caroline [0000-0003-4233-882X], Radice, Paolo [0000-0001-6298-4111], Robson, Mark [0000-0002-3109-1692], Rump, Andreas [0000-0001-7116-6364], Sharif, Saba [0000-0002-9564-4890], Steele, Linda [0000-0003-3628-2022], Stoppa-Lyonnet, Dominique [0000-0002-5438-8309], Teixeira, Manuel R [0000-0002-4896-5982], Thull, Darcy L [0000-0001-7999-2804], Tischkowitz, Marc [0000-0002-7880-0628], Toland, Amanda E [0000-0002-0271-1792], Tommasi, Stefania [0000-0002-2157-2978], Toss, Angela [0000-0002-1854-6701], Tripathi, Vishakha [0000-0001-8118-8364], Valentini, Virginia [0000-0003-3393-7185], van Asperen, Christi J [0000-0002-1436-7650], Venturelli, Marta [0000-0003-0658-8004], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Whaite, Anna [0000-0003-4485-0341], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Chenevix-Trench, Georgia [0000-0002-1878-2587], Ottini, Laura [0000-0001-8030-0449], and Apollo - University of Cambridge Repository

Subjects
Aged, 80 and over, BRCA2 Protein, Male, Heterozygote, BRCA1 Protein, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Mutation, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases
Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

39. Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Rolfes, Muriel, primary, Borde, Julika, additional, Möllenhoff, Kathrin, additional, Kayali, Mohamad, additional, Ernst, Corinna, additional, Gehrig, Andrea, additional, Sutter, Christian, additional, Ramser, Juliane, additional, Niederacher, Dieter, additional, Horváth, Judit, additional, Arnold, Norbert, additional, Meindl, Alfons, additional, Auber, Bernd, additional, Rump, Andreas, additional, Wang-Gohrke, Shan, additional, Ritter, Julia, additional, Hentschel, Julia, additional, Thiele, Holger, additional, Altmüller, Janine, additional, Nürnberg, Peter, additional, Rhiem, Kerstin, additional, Engel, Christoph, additional, Wappenschmidt, Barbara, additional, Schmutzler, Rita K., additional, Hahnen, Eric, additional, and Hauke, Jan, additional

Published
2022
Full Text
View/download PDF

40. Sustained response to bevacizumab in a patient with mosaic neurofibromatosis type 2 carrying the NF2:c.784C>T p.(Arg262*) variant

Author

Basenach, Elena, primary, Förster, Alisa, additional, Raab, Peter, additional, Alzein, Samer, additional, Schmidt, Gunnar, additional, Krauss, Joachim K., additional, Schlegelberger, Brigitte, additional, Heidenreich, Fedor, additional, Auber, Bernd, additional, Hartmann, Christian, additional, Wiese, Bettina, additional, and Weber, Ruthild G., additional

Published
2022
Full Text
View/download PDF

41. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Ottini, Laura, Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., and Ottini, Laura

Abstract

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

42. GenOtoScope: Towards automating ACMG classification of variants associated with congenital hearing loss

Author

Melidis, Damianos P., Landgraf, Christian, Schmidt, Gunnar, Schöner-Heinisch, Anja, Hardenberg, Sandra von, Lesinski-Schiedat, Anke, Nejdl, Wolfgang, Auber, Bernd, Melidis, Damianos P., Landgraf, Christian, Schmidt, Gunnar, Schöner-Heinisch, Anja, Hardenberg, Sandra von, Lesinski-Schiedat, Anke, Nejdl, Wolfgang, and Auber, Bernd

Abstract

Since next-generation sequencing (NGS) has become widely available, large gene panels containing up to several hundred genes can be sequenced cost-efficiently. However, the interpretation of the often large numbers of sequence variants detected when using NGS is laborious, prone to errors and is often difficult to compare across laboratories. To overcome this challenge, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) have introduced standards and guidelines for the interpretation of sequencing variants. Additionally, disease-specific refinements have been developed that include accurate thresholds for many criteria, enabling highly automated processing. This is of particular interest for common but heterogeneous disorders such as hearing impairment. With more than 200 genes associated with hearing disorders, the manual inspection of possible causative variants is particularly difficult and time-consuming. To this end, we developed the open-source bioinformatics tool GenOtoScope, which automates the analysis of all ACMG/AMP criteria that can be assessed without further individual patient information or human curator investigation, including the refined loss of function criterion (“PVS1”). Two types of interfaces are provided: (i) a command line application to classify sequence variants in batches for a set of patients and (ii) a user-friendly website to classify single variants. We compared the performance of our tool with two other variant classification tools using two hearing loss data sets, which were manually annotated either by the ClinGen Hearing Loss Gene Curation Expert Panel or the diagnostics unit of our human genetics department. GenOtoScope achieved the best average accuracy and precision for both data sets. Compared to the second-best tool, GenOtoScope improved the accuracy metric by 25.75% and 4.57% and precision metric by 52.11% and 12.13% on the two data sets, respectively. The web interfac

Published
2022

43. Prevalence of Cancer Predisposition Germline Variants in Male Breast Cancer Patients: Results of the German Consortium for Hereditary Breast and Ovarian Cancer

Author

Rolfes, Muriel, Borde, Julika, Moellenhoff, Kathrin, Kayali, Mohamad, Ernst, Corinna, Gehrig, Andrea, Sutter, Christian, Ramser, Juliane, Niederacher, Dieter, Horvath, Judit, Arnold, Norbert, Meindl, Alfons, Auber, Bernd, Rump, Andreas, Wang-Gohrke, Shan, Ritter, Julia, Hentschel, Julia, Thiele, Holger, Altmueller, Janine, Nuernberg, Peter, Rhiem, Kerstin, Engel, Christoph, Wappenschmidt, Barbara, Schmutzler, Rita K., Hahnen, Eric, Hauke, Jan, Rolfes, Muriel, Borde, Julika, Moellenhoff, Kathrin, Kayali, Mohamad, Ernst, Corinna, Gehrig, Andrea, Sutter, Christian, Ramser, Juliane, Niederacher, Dieter, Horvath, Judit, Arnold, Norbert, Meindl, Alfons, Auber, Bernd, Rump, Andreas, Wang-Gohrke, Shan, Ritter, Julia, Hentschel, Julia, Thiele, Holger, Altmueller, Janine, Nuernberg, Peter, Rhiem, Kerstin, Engel, Christoph, Wappenschmidt, Barbara, Schmutzler, Rita K., Hahnen, Eric, and Hauke, Jan

Abstract

Simple Summary Male breast cancer (mBC) is a rare disease associated with a high prevalence of pathogenic germline variants (PVs) in the BRCA2 gene. However, data regarding other breast cancer (BC) predisposition genes are limited or conflicting. We investigated the prevalence of PVs in BRCA1/2 and 23 other cancer predisposition genes using an overall study sample of 614 patients with mBC. A high proportion of patients with mBC carried pathogenic germline variants in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). A BRCA1/2 PV prevalence of 11.0% was identified in patients with mBC without a family history of breast and/or ovarian cancer. Patients with BRCA1/2 PVs did not show an earlier disease onset than those without. Case-control analyses revealed significant associations of protein-truncating variants in BRCA1, BRCA2, CHEK2, PALB2, and ATM with mBC. Our findings support the benefit of multi-gene panel testing in patients with mBC. Male breast cancer (mBC) is associated with a high prevalence of pathogenic variants (PVs) in the BRCA2 gene; however, data regarding other BC predisposition genes are limited. In this retrospective multicenter study, we investigated the prevalence of PVs in BRCA1/2 and 23 non-BRCA1/2 genes using a sample of 614 patients with mBC, recruited through the centers of the German Consortium for Hereditary Breast and Ovarian Cancer. A high proportion of patients with mBC carried PVs in BRCA2 (23.0%, 142/614) and BRCA1 (4.6%, 28/614). The prevalence of BRCA1/2 PVs was 11.0% in patients with mBC without a family history of breast and/or ovarian cancer. Patients with BRCA1/2 PVs did not show an earlier disease onset than those without. The predominant clinical presentation of tumor phenotypes was estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and HER2-negative (77.7%); further, 10.2% of the tumors were triple-positive, and 1.2% were triple-negative. No association was found between ER/PR/HER2 status and BRCA1/2 PV occurr

Published
2022

47. Genetics in inborn errors of immunity: pediatric autoinflammatory phenotypes and the underlying genetic causes in 125 families

Author

Poker, Yvonne, primary, von Hardenberg, Sandra, additional, Hofmann, Winfried, additional, Tang, Ming, additional, Baumann, Ulrich, additional, Schwerk, Nicolaus, additional, Wetzke, Martin, additional, Lindenthal, Viola, additional, Auber, Bernd, additional, Schlegelberger, Brigitte, additional, Ott, Hagen, additional, von Bismarck, Philipp, additional, Viemann, Dorothee, additional, Dressler, Frank, additional, Klemann, Christian, additional, and Bergmann, Anke Katharina, additional

Published
2022
Full Text
View/download PDF

49. CTLA-4 Insufficiency due to a Novel CTLA-4 Deletion, Identified through Copy Number Variation Analysis.

Author

Olfe, Lisa, von Hardenberg, Sandra, Hofmann, Winfried, Auber, Bernd, Baumann, Ulrich, Beier, Rita, Adriawan, Ignatius Ryan, Atschekzei, Faranaz, Witte, Torsten, and Sogkas, Georgios

Subjects
CYTOTOXIC T lymphocyte-associated molecule-4, SINGLE nucleotide polymorphisms, JUVENILE idiopathic arthritis, DNA copy number variations, NUCLEOTIDE sequencing
Abstract

Background: The diagnostic yield of next-generation sequencing (NGS) technologies in the diagnosis of monogenic inborn errors of immunity (IEI) remains limited, rarely exceeding 30%. Monoallelic pathogenic germline variants in cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) result in variable immunodeficiency and immune dysregulation. The genetic diagnosis of CTLA-4 insufficiency can affect follow-up procedures and may lead to consideration of treatment with CTLA-4-Ig. Objectives: The aim of the study was to identify the genetic cause of familial immunodeficiency and immune dysregulation in cases where single nucleotide variant analysis of short-read NGS data yielded no diagnostic result. Methods: Analysis of copy number variants (CNVs) was applied on short-read NGS data. Results: We identified a novel monoallelic deletion-insertion variant in CTLA-4 (c.445_568-544delinsTTTGCGATTG) resulting in familial autoimmunity. This is the second larger scale variant in CTLA-4, which despite consistently reduced expression of CTLA-4 displayed variable expressivity, ranging from typical juvenile idiopathic arthritis to common variable immunodeficiency-like immunodeficiency. Conclusions: Our report suggests the significance of integration of CNV analysis in routine evaluation of NGS, which may increase its diagnostic yield in IEI. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results