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...

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Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p10318
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10318
https://ddd.uab.cat/record/277657
Access Level:acceso abierto
Palabra clave: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
Computational Biology
Exome
Genomics
Humans
Rare Diseases
Whole Exome Sequencing
Descripción
Sumario: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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