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2022-05

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cc-by-nc-nd (c) American Society for Investigative Pathology and the Association for Molecular Pathology, 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/194746

Systematic collaborative reanalysis of genomic data improves diagnostic yield in neurologic rare diseases

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https://doi.org/10.1016/j.jmoldx.2022.02.003

Resum

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%).

Matèries

Malalties rares, Malalties del sistema nerviós, Genòmica

Matèries (anglès)

Rare diseases, Nervous system Diseases, Genomics

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Articles publicats en revistes (Genètica, Microbiologia i Estadística)

Citació

BULLICH, Gemma, MATALONGA, Leslie, PUJADAS, Montserrat, PAPAKONSTANTINOU, Anastasios, PISCIA, Davide, TONDA, Raúl, ARTUCH, Rafael, GALLANO, Pia, GARRABOU TORNOS, Glòria, GONZÁLEZ, Juan r., GRINBERG VAISMAN, Daniel raúl, GUITART, Míriam, LAURIE, Steven, LÁZARO GARCÍA, Conxi, LUENGO, Critina, MARTÍ, Ramon, MILÀ, Montserrat, OVELLEIRO, David, PARRA, Genís, PUJOL, Aurora, TIZZANO FERRARI, Eduardo, MACAYA, Alfonso, PALAU, Francesc, RIBES, Antonio, PÉREZ-JURADO, Luis alberto, BELTRAN, Sergi, Undiagnosed Rare Disease Program of Catalonia (URD-Cat) Consortium., RABIONET JANSSEN, Raquel, BALCELLS COMAS, Susana. Systematic collaborative reanalysis of genomic data improves diagnostic yield in neurologic rare diseases. _Journal of Molecular Diagnostics_. 2022. Vol. 24, núm. 5, pàgs. 529-542. [consulta: 21 de gener de 2026]. ISSN: 1525-1578. [Disponible a: https://hdl.handle.net/2445/194746]

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