A flexible computational pipeline for research analyses of unsolved clinical exome cases.

Autor: Lassmann T; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia. Timo.Lassmann@telethonkids.org.au., Francis RW; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Weeks A; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Tang D; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Jamieson SE; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Broley S; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Dawkins HJS; Office of Population Health Genomics, Public Health Division, Department of Health, Government of Western Australia, Perth, WA, Australia., Dreyer L; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Goldblatt J; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Groza T; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Kamien B; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Kiraly-Borri C; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., McKenzie F; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.; Faculty of Health and Medical Sciences, Division of Pediatrics, University of Western Australia, Perth, WA, Australia., Murphy L; Rare Voices Australia, Sydney, Australia., Pachter N; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Pathak G; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Poulton C; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Samanek A; GaRDN Genetics and Rare Diseases Network, Booragoon, WA, Australia., Skoss R; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia., Slee J; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Townshend S; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Ward M; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia., Baynam GS; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.; Genetic Services of Western Australia, Department of Health, Government of Western Australia, Perth, WA, Australia.; Faculty of Health and Medical Sciences, Division of Pediatrics, University of Western Australia, Perth, WA, Australia.; Western Australian Register of Developmental Anomalies, Department of Health, Government of Western Australia, Perth, WA, Australia., Blackwell JM; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia. Jenefer.Blackwell@telethonkids.org.au.
Jazyk: angličtina
Zdroj: NPJ genomic medicine [NPJ Genom Med] 2020 Dec 10; Vol. 5 (1), pp. 54. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1038/s41525-020-00161-w
Abstrakt: Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar. The pipeline ranked 21/34 previously diagnosed variants as top, with 26 in total ranked ≤7th, 3 ranked ≥13th; 5 failed the pipeline filters. Pathogenic/likely pathogenic variants by ACMG criteria were identified for 22/145 unsolved cases, and a previously undefined candidate disease variant for 27/145. This open access pipeline supports the partnership between clinical and research laboratories to improve the diagnosis of unsolved exomes. It provides a flexible framework for iterative developments to further improve diagnosis.
Databáze: MEDLINE