Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases.
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 reinterpreta...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2022 |
| País: | España |
| Recursos: | Institut d'Investigació i Innovació Parc Taulí (I3PT) |
| Repositório: | r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí |
| OAI Identifier: | oai:i3pt.fundanetsuite.com:p1540 |
| Acesso em linha: | https://i3pt.portalinvestigacion.com/publicaciones/1540 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85129716393&doi=10.1016%2fj.jmoldx.2022.02.003&partnerID=40&md5=c9b38d123b890e9a622b4f0023e8f719 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Computational Biology Exome Genomics Humans Rare Diseases Whole Exome Sequencing Article autism bioinformatics Catalonia cohort analysis consanguinity copy number variation data analysis degenerative disease diagnostic value epilepsy exome female genetic association genetic susceptibility genome genome analysis genomics heterozygosity homozygosity human indel mutation intellectual impairment major clinical study male metabolic disorder molecular diagnosis motor dysfunction neurologic disease neuromuscular disease phenotype rare disease single nucleotide polymorphism biology genetics whole exome sequencing |
| Resumo: | 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%). |
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