Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases
Por:
Bullich G., Matalonga L., Pujadas M., Papakonstantinou A., Piscia D., Tonda R., Artuch R., Gallano P., Garrabou G., González J.R., Grinberg D., Guitart M., Laurie S., Lázaro C., Luengo C., Martí R., Milà M., Ovelleiro D., Parra G., Pujol A., Tizzano E., Macaya A., Palau F., Ribes A., Pérez-Jurado L.A., Beltran S., Schlüter A., Rodriguez-Palmero A., Cáceres A., Nascimento A., García-Cazorla À., Cueto-González A., Marcé-Grau A., Nel.lo A.R., Martínez-Monseny A., Sànchez A., García B., Pérez-Dueñas B., Gel B., Fusté B., Hernández-Ferrer C., Casasnovas C., Ortez C., Arjona C., Hernando-Davalillo C., de Benito D.N., Amador D.P., Gómez-Andrés D., Yubero D., Pelegrí-Sisó D., Verdura E., García-Arumí E., Castellanos E., Gabau E., Tobías E., López-Grondona F., Cardellach F., Garcia-Garcia F.J., Munell F., Tort F., Aznar G., Olivé-Cirera G., Tell G., Muñoz-Pujol G., Paramonov I., Blanco I., Madrigal I., Valenzuela I., Gut I., Cusco I., Trotta J.-R., Cruz J., Díaz-Manera J., Milisenda J.C., Ma Grau J., Garcia-Villoria J., Armstrong J., Cantó J., Sala-Coromina J., Rodríguez-Revenga L., Alias L., Gort L., González-Quereda L., Costa M., Fernández-Callejo M., López-Sánchez M., Álvarez-Mora M.I., Gut M., Serrano M., Raspall-Chaure M., Toro M.D., Bayés M., Díez N.B., Spataro N., Capdevila N., Ugarteburu O., Muñoz-Cabello P., Duque P.R., Rabionet R., Rojas-García R., Calvo R., Urreizti R., Bernal S., Boronat S., Balcells S., Vendrell T.
Publicada:
1 may 2022
Ahead of Print:
1 may 2022
Resumen:
Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7% ), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%).
Filiaciones:
Bullich G.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Matalonga L.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Pujadas M.:
Genetics Unit, University Pompeu Fabra, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
Papakonstantinou A.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Piscia D.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Tonda R.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Artuch R.:
Clinical Biochemistry Department, Institut de Recerca Sant Joan de Déu (IRSJD), Barcelona, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Gallano P.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Genetics Department, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Garrabou G.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Muscle Research and Mitochondrial Function Laboratory, CELLEX-Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Internal Medicine Department, Hospital Clinic of Barcelona, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
González J.R.:
Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain
Universitat Pompeu Fabra, Barcelona, Spain
Centro de Investigaciones Biomédicas en Red de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
Grinberg D.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Institut de Recerca Sant Joan de Déu (IRSJD), Barcelona, Spain
Guitart M.:
Genetics Laboratory, Paediatric Unit, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain
Laurie S.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Lázaro C.:
Molecular Diagnostic Unit, Hereditary Cancer Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Catalan Institute of Oncology, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain
Luengo C.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Martí R.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Research Group on Neuromuscular and Mitochondrial Diseases, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
Milà M.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Biochemistry and Molecular Genetics Department, Hospital Clínic de Barcelona, Institut d'Investigació Biomèdica August Pi I Sunyer (IDIBAPS), Barcelona, Spain
Ovelleiro D.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Parra G.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Pujol A.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Neurometabolic Diseases Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)–Hospital Duran i Reynals, Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
Tizzano E.:
Department of Clinical and Molecular Genetics, Medicine Genetics Group Vall d'Hebron Institut de Recerca (VHIR), European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA, Universitat Autònoma de Barcelona, Hospital Vall d´Hebron, Barcelona, Spain
Macaya A.:
Pediatric Neurology Research Group, Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
Palau F.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Department of Genetic and Molecular Medicine, Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Clinic Institute of Medicine and Dermatology, Hospital Clínic de Barcelona and Division of Pediatrics, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Ribes A.:
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Secció d'Errors Congènits del Metabolisme–Institute of Clinical Biochemistry (IBC), Servei de Bioquímica i Genètìca Molecular, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Pérez-Jurado L.A.:
Genetics Unit, University Pompeu Fabra, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Women's and Children's Hospital, South Australian Health and Medical Research Institute and The University of Adelaide, Adelaide, SA, Australia
Beltran S.:
Centro Nacional Análisis Genómico (CNAG)–Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
Universitat Pompeu Fabra, Barcelona, Spain
Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
Green Published, hybrid, All Open Access; Hybrid Gold
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