Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon

Angelica Maria Delgado-Vega^#^{1

2}, Helene Cederroth^#³, Fulya Taylan^#^{4

5}, Katja Ekholm^{4

5}, Marlene Ek^{4

5}, Håkan Thonberg^{4

5}, Anders Jemt^{6

7}, Daniel Nilsson^{4

8}, Jesper Eisfeldt^{4

8}, Kristine Bilgrav Saether⁸, Ida Höijer^{9

10}, Ozlem Akgun-Dogan^{11

12

13}, Yui Asano¹⁴, Tahsin Stefan Barakat^{15

16

17}, Dominyka Batkovskyte⁵, Gareth Baynam^{18

19

20

21}, Olaf Bodamer²², Wanna Chetruengchai^{23

24}, Pádraic Corcoran^{9

10}, Madeline Couse²⁵, Daniel Danis²⁶, German Demidov²⁷, Eisuke Dohi²⁸, Mattias Erhardsson²⁹, Luis Fernandez-Luna³⁰, Toyofumi Fujiwara³¹, Neha Garg³², Roberto Giugliani^{33

34

35

36}, Claudia Gonzaga-Jauregui³⁰, Giedre Grigelioniene^{4

5}, Tudor Groza^{18

37

38

39}, Cecilia Gunnarsson⁴⁰, Anna Hammarsjö^{4

5}, Charles Kumi Hammond^{11

41}, Özden Hatirnaz Ng^{12

13

42}, Sirisha Hesketh⁴³, Dineshani Hettiarachchi⁴⁴, Maria Johansson Soller^{4

5}, Umn Ahmed Kirmani⁴⁵, Martin Kjellberg⁴⁶, Malin Kvarnung^{4

5}, Oleg Kvlividze^{47

48}, Kristina Lagerstedt-Robinson^{4

5}, Paul Lasko⁴⁹, Timo Lassmann⁵⁰, Lynette Y S Lau⁵¹, Steven Laurie^{52

53}, Weng Khong Lim^{37

54

55

56}, Zhandong Liu⁵⁷, Mariya Lysenkova Wiklander^{10

58}, Prince Makay⁵⁹, Alassane Baneye Maiga⁶⁰, Carolina Maya-González⁵, M Stephen Meyn^{61

62}, Ramprasad Neethiraj^{6

63}, Vincenzo Nigro^{64

65}, Felix Nordgren⁶⁶, Jessica Nordlund^{10

58}, Sara Orrsjö^{67

68}, Jesper Ottosson^{67

68}, Ugur Ozbek^{12

69}, Özkan Özdemir^{12

42}, Clyde Partin^{70

71}, David A Pearce^{72

73

74

75}, Raquel Peck⁷⁶, Annie Pedersen^{67

68}, Maria Pettersson^{4

5}, Monnat Pongpanich^{77

78}, Manuel Posada de la Paz^{79

80}, Arun Ramani⁸¹, Juan Andres Romero⁸², Vanessa I Romero⁸², Richard Rosenquist^{4

5

7}, Aung Min Saw^{83

84}, Matthew Spencer⁸³, Eva-Lena Stattin⁸⁵, Chalurmpon Srichomthong^{23

24}, Isabel Tapia-Paez⁸⁶, Domenica Taruscio^{87

88}, Julie P Taylor⁸⁹, Tinatin Tkemaladze^{90

91

92}, Ian Tully^{83

93}, Zeynep Tümer^{94

95}, Wendy A G van Zelst-Stams⁹⁶, Alain Verloes^{97

98}, Emma Västerviga^{99

100}, Sailan Wang⁸⁶, Rachel Yang^{101

102}, Shinya Yamamoto^{103

104}, Vicente A Yépez¹⁰⁵, Qing Zhang⁸⁹, Vorasuk Shotelersuk^{23

24}, Samuel Agyei Wiafe¹⁰⁶, Yasemin Alanay^{11

12

13}, Lorenzo D Botto¹⁰⁷, Salman Kirmani¹⁰⁸, Aimé Lumaka^{59

109

110}, Elizabeth Emma Palmer^{111

112}, Ratna Dua Puri^{32

113}, Valtteri Wirta^{4

6}, Anna Lindstrand^{4

5}, Orion J Buske¹¹⁴, Mikk Cederroth³, Ann Nordgren^{115

116

117

118}

Affiliations

¹ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden. angelica.delgado.vega@ki.se.
² Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. angelica.delgado.vega@ki.se.
³ Wilhelm Foundation, Brottby, Sweden.
⁴ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden.
⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁶ Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
⁷ Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
⁸ Science for Life Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
¹⁰ Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹¹ Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem University, Istanbul, Turkey.
¹² ACURARE, Acibadem University Rare Diseases and Orphan Drugs Application and Research Center, Istanbul, Turkey.
¹³ Department of Medical Genetics, Acibadem University, Istanbul, Turkey.
¹⁴ Swallow Design Studio, Tokyo, Japan.
¹⁵ Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
¹⁶ Discovery Unit, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
¹⁷ ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, the Netherlands.
¹⁸ Rare Care Centre, Perth Children's Hospital, Perth, Western Australia, Australia.
¹⁹ Western Australian Register of Developmental Anomalies, Perth, Western Australia, Australia.
²⁰ Undiagnosed Diseases Program, Genetic Health WA, King Edward Memorial Hospital, Perth, Western Australia, Australia.
²¹ Faculty of Medicine, Australian National University, Perth, Western Australia, Australia.
²² Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
²³ Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
²⁴ Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand.
²⁵ Centre for Computational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
²⁶ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
²⁷ Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
²⁸ National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
²⁹ Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³⁰ International Laboratory for Human Genome Research, Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.
³¹ Database Center for Life Science, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, Chiba, Japan.
³² Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India.
³³ Casa dos Raros, Porto Alegre, Brazil.
³⁴ Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
³⁵ Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
³⁶ Dasa Genomica, São Paulo, Brazil.
³⁷ SingHealth Duke-NUS Institute of Precision Medicine, Singapore, Singapore.
³⁸ Telethon Kids Institute, Perth, Western Australia, Australia.
³⁹ School of Electrical Engineering, Computing and Mathematical Sciences, Curtin University, Perth, Western Australia, Australia.
⁴⁰ Department of Clinical Genetics, Department of Biomedical and Clinical Sciences, Centre for Rare Diseases in Southeast Region of Sweden, Linköping University, Linköping, Sweden.
⁴¹ Department of Child Health, Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
⁴² Department of Medical Biology, School of Medicine, Acibadem University, Istanbul, Turkey.
⁴³ Oxford Nanopore Technologies, Oxford, UK.
⁴⁴ Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
⁴⁵ Karachi Grammar School, Karachi, Pakistan.
⁴⁶ KTH Royal Institute of Technology, Stockholm, Sweden.
⁴⁷ School of Medicine, New Vision University, Tbilisi, Georgia.
⁴⁸ Georgian Foundation for Genetic and Rare Diseases, Tbilisi, Georgia.
⁴⁹ Department of Biology, McGill University, Montreal, Quebec, Canada.
⁵⁰ Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
⁵¹ Genome Diagnostic, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁵² Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
⁵³ Universitat de Barcelona (UB), Barcelona, Spain.
⁵⁴ Cancer & Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore.
⁵⁵ SingHealth Duke-NUS Genomic Medicine Centre, Singapore, Singapore.
⁵⁶ Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
⁵⁷ Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
⁵⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁵⁹ Centre for Human Genetics, University of Kinshasa, Kinshasa, DR, Congo.
⁶⁰ Faculté de Médecine et d'Odontostomatologie, Université des Sciences, des Techniques et des Technologies de Bamako, Bamako, Mali.
⁶¹ Center for Human Genomics and Precision Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁶² Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
⁶³ School of Engineering Science in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
⁶⁴ Department of Precision Medicine, Università della Campania Luigi Vanvitelli, Naples, Italy.
⁶⁵ TIGEM (Telethon Institute of Genetics and Medicine), Naples, Italy.
⁶⁶ Department of Management and Engineering, Linköping University, Linköping, Sweden.
⁶⁷ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶⁸ Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶⁹ Rare and Undiagnosed Disease Platform-RUDiP, Izmir Biomedicine and Genome Center-IBG, Izmir, Turkey.
⁷⁰ Medicine, Emory Healthcare, Emory University, Atlanta, GA, USA.
⁷¹ Emory Special Diagnostic Services Clinic, Emory University School of Medicine, Atlanta, GA, USA.
⁷² Sanford Research, Sioux Falls, SD, USA.
⁷³ Sanford Health, Sioux Falls, SD, USA.
⁷⁴ Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
⁷⁵ International Rare Disease Research Consortium (IRDiRC).
⁷⁶ Clarion I, London, UK.
⁷⁷ Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
⁷⁸ Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
⁷⁹ SpainUDP, Rare Diseases Research Institute, Instituto de Salud Carlos III, Madrid, Spain.
⁸⁰ FCSAI, Madrid, Spain.
⁸¹ Invitae, San Francisco, CA, USA.
⁸² Universidad San Francisco de Quito, Quito, Ecuador.
⁸³ The Syndrome Without A Name (SWAN) Clinic, University Hospital of Wales, Cardiff, UK.
⁸⁴ Department of Neurology, University Hospital of Wales, Cardiff, UK.
⁸⁵ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
⁸⁶ Division of Dermatology and Venereology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
⁸⁷ National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
⁸⁸ Study Centre KOS-Science, Art, Society, Rome, Italy.
⁸⁹ Illumina Inc, San Diego, CA, USA.
⁹⁰ Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia.
⁹¹ Department of Pediatrics, Givi Zhvania Pediatric Academic Clinic, Tbilisi State Medical University, Tbilisi, Georgia.
⁹² Center for Undiagnosed and Rare Diseases, Tbilisi State Medical University, Tbilisi, Georgia.
⁹³ Department of Clinical Genetics, University Hospital of Wales, Cardiff, UK.
⁹⁴ Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁹⁵ Department of Clinical Medicine, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹⁶ Department of Human Genetics, Radboud Institute for Health Science, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹⁷ ERN-ITHACA European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders.
⁹⁸ Department of Clinical Genetics, Robert-Debré Hospital, Paris, France.
⁹⁹ Bioinformatics and Data Centre, Gothenburg University, Gothenburg, Sweden.
¹⁰⁰ Bioinformatics and Data Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁰¹ Rare Diseases Center, Zhongshan Hospital, Fudan University, Shanghai, China.
¹⁰² China Alliance for Rare Diseases, Beijing, China.
¹⁰³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
¹⁰⁴ Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
¹⁰⁵ School of Computation, Information and Technology, Technical University of Munich, Garching, Germany.
¹⁰⁶ Rare Disease Ghana Initiative, Accra, Ghana.
¹⁰⁷ Division of Medical Genetics, Dept of Pediatrics, University of Utah, Salt Lake City, UT, USA.
¹⁰⁸ Division of Women & Child Health, Aga Khan University, Karachi, Pakistan.
¹⁰⁹ Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, DR, Congo.
¹¹⁰ African Rare Diseases Initiative.
¹¹¹ Discipline of Paediatrics and Child Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
¹¹² Centre for Clinical Genetics, Sydney Children's Hospitals Network, Randwick, New South Wales, Australia.
¹¹³ Ganga Ram Institute of Postgraduate Medical Education and Research (GRIPMER), Sir Ganga Ram Hospital, New Delhi, India.
¹¹⁴ PhenoTips, Toronto, Ontario, Canada.
¹¹⁵ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden. ann.nordgren@ki.se.
¹¹⁶ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. ann.nordgren@ki.se.
¹¹⁷ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden. ann.nordgren@ki.se.
¹¹⁸ Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ann.nordgren@ki.se.

^# Contributed equally.

PMID: 39433890
PMCID: PMC12198426
DOI: 10.1038/s41588-024-01941-1

Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon

Angelica Maria Delgado-Vega et al. Nat Genet. 2024 Nov.

. 2024 Nov;56(11):2287-2294.

doi: 10.1038/s41588-024-01941-1.

Authors

Affiliations

¹ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden. angelica.delgado.vega@ki.se.
² Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. angelica.delgado.vega@ki.se.
³ Wilhelm Foundation, Brottby, Sweden.
⁴ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden.
⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁶ Science for Life Laboratory, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
⁷ Genomic Medicine Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
⁸ Science for Life Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
¹⁰ Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹¹ Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem University, Istanbul, Turkey.
¹² ACURARE, Acibadem University Rare Diseases and Orphan Drugs Application and Research Center, Istanbul, Turkey.
¹³ Department of Medical Genetics, Acibadem University, Istanbul, Turkey.
¹⁴ Swallow Design Studio, Tokyo, Japan.
¹⁵ Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
¹⁶ Discovery Unit, Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
¹⁷ ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus Medical Center, Rotterdam, the Netherlands.
¹⁸ Rare Care Centre, Perth Children's Hospital, Perth, Western Australia, Australia.
¹⁹ Western Australian Register of Developmental Anomalies, Perth, Western Australia, Australia.
²⁰ Undiagnosed Diseases Program, Genetic Health WA, King Edward Memorial Hospital, Perth, Western Australia, Australia.
²¹ Faculty of Medicine, Australian National University, Perth, Western Australia, Australia.
²² Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
²³ Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
²⁴ Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand.
²⁵ Centre for Computational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
²⁶ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
²⁷ Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
²⁸ National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
²⁹ Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³⁰ International Laboratory for Human Genome Research, Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico.
³¹ Database Center for Life Science, Joint Support-Center for Data Science Research, Research Organization of Information and Systems, Chiba, Japan.
³² Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India.
³³ Casa dos Raros, Porto Alegre, Brazil.
³⁴ Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
³⁵ Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
³⁶ Dasa Genomica, São Paulo, Brazil.
³⁷ SingHealth Duke-NUS Institute of Precision Medicine, Singapore, Singapore.
³⁸ Telethon Kids Institute, Perth, Western Australia, Australia.
³⁹ School of Electrical Engineering, Computing and Mathematical Sciences, Curtin University, Perth, Western Australia, Australia.
⁴⁰ Department of Clinical Genetics, Department of Biomedical and Clinical Sciences, Centre for Rare Diseases in Southeast Region of Sweden, Linköping University, Linköping, Sweden.
⁴¹ Department of Child Health, Komfo Anokye Teaching Hospital, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
⁴² Department of Medical Biology, School of Medicine, Acibadem University, Istanbul, Turkey.
⁴³ Oxford Nanopore Technologies, Oxford, UK.
⁴⁴ Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.
⁴⁵ Karachi Grammar School, Karachi, Pakistan.
⁴⁶ KTH Royal Institute of Technology, Stockholm, Sweden.
⁴⁷ School of Medicine, New Vision University, Tbilisi, Georgia.
⁴⁸ Georgian Foundation for Genetic and Rare Diseases, Tbilisi, Georgia.
⁴⁹ Department of Biology, McGill University, Montreal, Quebec, Canada.
⁵⁰ Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
⁵¹ Genome Diagnostic, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁵² Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
⁵³ Universitat de Barcelona (UB), Barcelona, Spain.
⁵⁴ Cancer & Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore.
⁵⁵ SingHealth Duke-NUS Genomic Medicine Centre, Singapore, Singapore.
⁵⁶ Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
⁵⁷ Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
⁵⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁵⁹ Centre for Human Genetics, University of Kinshasa, Kinshasa, DR, Congo.
⁶⁰ Faculté de Médecine et d'Odontostomatologie, Université des Sciences, des Techniques et des Technologies de Bamako, Bamako, Mali.
⁶¹ Center for Human Genomics and Precision Medicine, University of Wisconsin-Madison, Madison, WI, USA.
⁶² Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA.
⁶³ School of Engineering Science in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
⁶⁴ Department of Precision Medicine, Università della Campania Luigi Vanvitelli, Naples, Italy.
⁶⁵ TIGEM (Telethon Institute of Genetics and Medicine), Naples, Italy.
⁶⁶ Department of Management and Engineering, Linköping University, Linköping, Sweden.
⁶⁷ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶⁸ Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶⁹ Rare and Undiagnosed Disease Platform-RUDiP, Izmir Biomedicine and Genome Center-IBG, Izmir, Turkey.
⁷⁰ Medicine, Emory Healthcare, Emory University, Atlanta, GA, USA.
⁷¹ Emory Special Diagnostic Services Clinic, Emory University School of Medicine, Atlanta, GA, USA.
⁷² Sanford Research, Sioux Falls, SD, USA.
⁷³ Sanford Health, Sioux Falls, SD, USA.
⁷⁴ Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
⁷⁵ International Rare Disease Research Consortium (IRDiRC).
⁷⁶ Clarion I, London, UK.
⁷⁷ Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
⁷⁸ Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
⁷⁹ SpainUDP, Rare Diseases Research Institute, Instituto de Salud Carlos III, Madrid, Spain.
⁸⁰ FCSAI, Madrid, Spain.
⁸¹ Invitae, San Francisco, CA, USA.
⁸² Universidad San Francisco de Quito, Quito, Ecuador.
⁸³ The Syndrome Without A Name (SWAN) Clinic, University Hospital of Wales, Cardiff, UK.
⁸⁴ Department of Neurology, University Hospital of Wales, Cardiff, UK.
⁸⁵ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
⁸⁶ Division of Dermatology and Venereology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
⁸⁷ National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy.
⁸⁸ Study Centre KOS-Science, Art, Society, Rome, Italy.
⁸⁹ Illumina Inc, San Diego, CA, USA.
⁹⁰ Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia.
⁹¹ Department of Pediatrics, Givi Zhvania Pediatric Academic Clinic, Tbilisi State Medical University, Tbilisi, Georgia.
⁹² Center for Undiagnosed and Rare Diseases, Tbilisi State Medical University, Tbilisi, Georgia.
⁹³ Department of Clinical Genetics, University Hospital of Wales, Cardiff, UK.
⁹⁴ Kennedy Center, Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁹⁵ Department of Clinical Medicine, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
⁹⁶ Department of Human Genetics, Radboud Institute for Health Science, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹⁷ ERN-ITHACA European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders.
⁹⁸ Department of Clinical Genetics, Robert-Debré Hospital, Paris, France.
⁹⁹ Bioinformatics and Data Centre, Gothenburg University, Gothenburg, Sweden.
¹⁰⁰ Bioinformatics and Data Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
¹⁰¹ Rare Diseases Center, Zhongshan Hospital, Fudan University, Shanghai, China.
¹⁰² China Alliance for Rare Diseases, Beijing, China.
¹⁰³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
¹⁰⁴ Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
¹⁰⁵ School of Computation, Information and Technology, Technical University of Munich, Garching, Germany.
¹⁰⁶ Rare Disease Ghana Initiative, Accra, Ghana.
¹⁰⁷ Division of Medical Genetics, Dept of Pediatrics, University of Utah, Salt Lake City, UT, USA.
¹⁰⁸ Division of Women & Child Health, Aga Khan University, Karachi, Pakistan.
¹⁰⁹ Department of Pediatrics, Faculty of Medicine, University of Kinshasa, Kinshasa, DR, Congo.
¹¹⁰ African Rare Diseases Initiative.
¹¹¹ Discipline of Paediatrics and Child Health, Faculty of Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia.
¹¹² Centre for Clinical Genetics, Sydney Children's Hospitals Network, Randwick, New South Wales, Australia.
¹¹³ Ganga Ram Institute of Postgraduate Medical Education and Research (GRIPMER), Sir Ganga Ram Hospital, New Delhi, India.
¹¹⁴ PhenoTips, Toronto, Ontario, Canada.
¹¹⁵ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden. ann.nordgren@ki.se.
¹¹⁶ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. ann.nordgren@ki.se.
¹¹⁷ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden. ann.nordgren@ki.se.
¹¹⁸ Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ann.nordgren@ki.se.

^# Contributed equally.

PMID: 39433890
PMCID: PMC12198426
DOI: 10.1038/s41588-024-01941-1

Abstract

The first-ever Undiagnosed Hackathon was a groundbreaking event held by the Wilhelm Foundation, the Karolinska Undiagnosed Disease Program, and PhenoTips in collaboration with UDNI to solve medical mysteries and advance diagnostics for undiagnosed rare diseases. Nearly 100 healthcare professionals and researchers from 28 countries participated, working intensively for 48 hours to diagnose 10 families with undiagnosed rare diseases. This innovative approach to precision diagnostics highlighted the power of international, multidisciplinary collaboration and patient partnership, yielding promising results for patients seeking answers and benefiting the entire rare diseases community.

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Figures

**Figure 1.**
Undiagnosed families from eight UDNI member countries were selected. After informed consent was obtained, blood samples were collected from patients and their families. DNA and RNA were sequenced using short-read whole genome and RNA sequencing, long-read genome and RNA sequencing and EPIC methylation array. Standardized deep phenotype data, together with the genomic data, were analyzed in multidisciplinary teams, which worked intensively for 48 hours to interpret the data. Four families received a diagnosis, candidate genes were found in four other families, and recommendations for further studies were provided for all undiagnosed cases. Undiagnosed Hackathon logo created by Yui Asano. Figure created with BioRender.com

See this image and copyright information in PMC

References

1. Ferreira CR The burden of rare diseases. Am J Med Genet A 179, 885–892 (2019). - PubMed
1. Smith CIE, Bergman P & Hagey DW Estimating the number of diseases - the concept of rare, ultra-rare, and hyper-rare. iScience 25, 104698 (2022). - PMC - PubMed
1. Nguengang Wakap S et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet 28, 165–173 (2020). - PMC - PubMed
1. Wright CF et al. Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland. N Engl J Med 388, 1559–1571 (2023). - PMC - PubMed
1. Edsjo A et al. Building a precision medicine infrastructure at a national level: The Swedish experience. Camb Prism Precis Med 1, e15 (2023). - PMC - PubMed

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Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon

Affiliations

Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon

Authors

Affiliations

Abstract

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources