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Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases
Up to 350 million people worldwide suffer from a rare disease, and while the individual diseases are rare, in aggregate they represent a substantial challenge to global health systems. The majority of rare disorders are genetic in origin, with children under the age of five disproportionately affect...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929710/ https://www.ncbi.nlm.nih.gov/pubmed/31023718 http://dx.doi.org/10.1136/jmedgenet-2019-106111 |
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author | Bick, David Jones, Marilyn Taylor, Stacie L Taft, Ryan J Belmont, John |
author_facet | Bick, David Jones, Marilyn Taylor, Stacie L Taft, Ryan J Belmont, John |
author_sort | Bick, David |
collection | PubMed |
description | Up to 350 million people worldwide suffer from a rare disease, and while the individual diseases are rare, in aggregate they represent a substantial challenge to global health systems. The majority of rare disorders are genetic in origin, with children under the age of five disproportionately affected. As these conditions are difficult to identify clinically, genetic and genomic testing have become the backbone of diagnostic testing in this population. In the last 10 years, next-generation sequencing technologies have enabled testing of multiple disease genes simultaneously, ranging from targeted gene panels to exome sequencing (ES) and genome sequencing (GS). GS is quickly becoming a practical first-tier test, as cost decreases and performance improves. A growing number of studies demonstrate that GS can detect an unparalleled range of pathogenic abnormalities in a single laboratory workflow. GS has the potential to deliver unbiased, rapid and accurate molecular diagnoses to patients across diverse clinical indications and complex presentations. In this paper, we discuss clinical indications for testing and historical testing paradigms. Evidence supporting GS as a diagnostic tool is supported by superior genomic coverage, types of pathogenic variants detected, simpler laboratory workflow enabling shorter turnaround times, diagnostic and reanalysis yield, and impact on healthcare. |
format | Online Article Text |
id | pubmed-6929710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-69297102020-01-06 Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases Bick, David Jones, Marilyn Taylor, Stacie L Taft, Ryan J Belmont, John J Med Genet Diagnostics Up to 350 million people worldwide suffer from a rare disease, and while the individual diseases are rare, in aggregate they represent a substantial challenge to global health systems. The majority of rare disorders are genetic in origin, with children under the age of five disproportionately affected. As these conditions are difficult to identify clinically, genetic and genomic testing have become the backbone of diagnostic testing in this population. In the last 10 years, next-generation sequencing technologies have enabled testing of multiple disease genes simultaneously, ranging from targeted gene panels to exome sequencing (ES) and genome sequencing (GS). GS is quickly becoming a practical first-tier test, as cost decreases and performance improves. A growing number of studies demonstrate that GS can detect an unparalleled range of pathogenic abnormalities in a single laboratory workflow. GS has the potential to deliver unbiased, rapid and accurate molecular diagnoses to patients across diverse clinical indications and complex presentations. In this paper, we discuss clinical indications for testing and historical testing paradigms. Evidence supporting GS as a diagnostic tool is supported by superior genomic coverage, types of pathogenic variants detected, simpler laboratory workflow enabling shorter turnaround times, diagnostic and reanalysis yield, and impact on healthcare. BMJ Publishing Group 2019-12 2019-04-25 /pmc/articles/PMC6929710/ /pubmed/31023718 http://dx.doi.org/10.1136/jmedgenet-2019-106111 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Diagnostics Bick, David Jones, Marilyn Taylor, Stacie L Taft, Ryan J Belmont, John Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
title | Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
title_full | Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
title_fullStr | Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
title_full_unstemmed | Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
title_short | Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
title_sort | case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases |
topic | Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929710/ https://www.ncbi.nlm.nih.gov/pubmed/31023718 http://dx.doi.org/10.1136/jmedgenet-2019-106111 |
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