Please use this identifier to cite or link to this item:
https://dipositint.ub.edu/dspace/handle/2445/194746
Title: | Systematic collaborative reanalysis of genomic data improves diagnostic yield in neurologic rare diseases |
Author: | 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, Conxi Luengo, Critina Martí, Ramon Milà, Montserrat Ovelleiro, David Parra, Genís Pujol, Aurora Tizzano, Eduardo Macaya, Alfonso Palau, Francesc Ribes, Antonio Pérez-Jurado, Luis A. Beltran, Sergi Undiagnosed Rare Disease Program of Catalonia (URD-Cat) Consortium. Rabionet Janssen, Raquel Balcells Comas, Susana |
Keywords: | Malalties rares Malalties del sistema nerviós Genòmica Rare diseases Nervous system Diseases Genomics |
Issue Date: | May-2022 |
Publisher: | American Society for Investigative Pathology and the Association for Molecular Pathology |
Abstract: | 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%). |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.jmoldx.2022.02.003 |
It is part of: | Journal of Molecular Diagnostics, 2022, vol. 24, num. 5, p. 529-542 |
URI: | http://hdl.handle.net/2445/194746 |
Related resource: | https://doi.org/10.1016/j.jmoldx.2022.02.003 |
ISSN: | 1525-1578 |
Appears in Collections: | Articles publicats en revistes (Genètica, Microbiologia i Estadística) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
723501.pdf | 1.06 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License