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Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases
Next-generation sequencing (NGS) has altered clinical genetic testing by widening the access to molecular diagnosis of genetically determined rare diseases. However, physicians may face difficulties selecting the best diagnostic approach. Our goal is to estimate the rate of possible molecular diagno...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Sociedade Brasileira de Genética
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485181/ https://www.ncbi.nlm.nih.gov/pubmed/34609444 http://dx.doi.org/10.1590/1678-4685-GMB-2021-0061 |
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author | Quaio, Caio Robledo D’Angioli Costa Obando, María José Rivadeneira Perazzio, Sandro Felix Dutra, Aurelio Pimenta Chung, Christine Hsiaoyun Moreira, Caroline Monaco Novo, Gil Monteiro Sacramento-Bobotis, Patricia Rossi Penna, Michele Groenner de Souza, Rafaela Rogerio Floriano Cintra, Vivian Pedigone Carnavalli, Juliana Emilia Prior da Silva, Rafael Alves Santos, Monize Nakamoto Provisor Paixão, Daniele Baratela, Wagner Antonio da Rosa Olivati, Caroline Spolador, Gustavo Marquezani Pintao, Maria Carolina Fornari, Alexandre Ricardo dos Santos Burger, Matheus Ramalho, Rodrigo Fernandes Pereira, Otavio Jose Eulalio Ferreira, Elisa Napolitano e Mitne-Neto, Miguel Kim, Chong Ae |
author_facet | Quaio, Caio Robledo D’Angioli Costa Obando, María José Rivadeneira Perazzio, Sandro Felix Dutra, Aurelio Pimenta Chung, Christine Hsiaoyun Moreira, Caroline Monaco Novo, Gil Monteiro Sacramento-Bobotis, Patricia Rossi Penna, Michele Groenner de Souza, Rafaela Rogerio Floriano Cintra, Vivian Pedigone Carnavalli, Juliana Emilia Prior da Silva, Rafael Alves Santos, Monize Nakamoto Provisor Paixão, Daniele Baratela, Wagner Antonio da Rosa Olivati, Caroline Spolador, Gustavo Marquezani Pintao, Maria Carolina Fornari, Alexandre Ricardo dos Santos Burger, Matheus Ramalho, Rodrigo Fernandes Pereira, Otavio Jose Eulalio Ferreira, Elisa Napolitano e Mitne-Neto, Miguel Kim, Chong Ae |
author_sort | Quaio, Caio Robledo D’Angioli Costa |
collection | PubMed |
description | Next-generation sequencing (NGS) has altered clinical genetic testing by widening the access to molecular diagnosis of genetically determined rare diseases. However, physicians may face difficulties selecting the best diagnostic approach. Our goal is to estimate the rate of possible molecular diagnoses missed by different targeted gene panels using data from a cohort of patients with rare genetic diseases diagnosed with exome sequencing (ES). For this purpose, we simulated a comparison between different targeted gene panels and ES: the list of genes harboring clinically relevant variants from 158 patients was used to estimate the theoretical rate of diagnoses missed by NGS panels from 53 different NGS panels from eight different laboratories. Panels presented a mean rate of missed diagnoses of 64% (range 14%-100%) compared to ES, representing an average predicted sensitivity of 36%. Metabolic abnormalities represented the group with highest mean of missed diagnoses (86%), while seizure represented the group with lowest mean (46%). Focused gene panels are restricted in covering select sets of genes implicated in specific diseases and they may miss molecular diagnoses of rare diseases compared to ES. However, their role in genetic diagnosis remains important especially for well-known genetic diseases with established genetic locus heterogeneity. |
format | Online Article Text |
id | pubmed-8485181 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Sociedade Brasileira de Genética |
record_format | MEDLINE/PubMed |
spelling | pubmed-84851812021-10-08 Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases Quaio, Caio Robledo D’Angioli Costa Obando, María José Rivadeneira Perazzio, Sandro Felix Dutra, Aurelio Pimenta Chung, Christine Hsiaoyun Moreira, Caroline Monaco Novo, Gil Monteiro Sacramento-Bobotis, Patricia Rossi Penna, Michele Groenner de Souza, Rafaela Rogerio Floriano Cintra, Vivian Pedigone Carnavalli, Juliana Emilia Prior da Silva, Rafael Alves Santos, Monize Nakamoto Provisor Paixão, Daniele Baratela, Wagner Antonio da Rosa Olivati, Caroline Spolador, Gustavo Marquezani Pintao, Maria Carolina Fornari, Alexandre Ricardo dos Santos Burger, Matheus Ramalho, Rodrigo Fernandes Pereira, Otavio Jose Eulalio Ferreira, Elisa Napolitano e Mitne-Neto, Miguel Kim, Chong Ae Genet Mol Biol Human and Medical Genetics Next-generation sequencing (NGS) has altered clinical genetic testing by widening the access to molecular diagnosis of genetically determined rare diseases. However, physicians may face difficulties selecting the best diagnostic approach. Our goal is to estimate the rate of possible molecular diagnoses missed by different targeted gene panels using data from a cohort of patients with rare genetic diseases diagnosed with exome sequencing (ES). For this purpose, we simulated a comparison between different targeted gene panels and ES: the list of genes harboring clinically relevant variants from 158 patients was used to estimate the theoretical rate of diagnoses missed by NGS panels from 53 different NGS panels from eight different laboratories. Panels presented a mean rate of missed diagnoses of 64% (range 14%-100%) compared to ES, representing an average predicted sensitivity of 36%. Metabolic abnormalities represented the group with highest mean of missed diagnoses (86%), while seizure represented the group with lowest mean (46%). Focused gene panels are restricted in covering select sets of genes implicated in specific diseases and they may miss molecular diagnoses of rare diseases compared to ES. However, their role in genetic diagnosis remains important especially for well-known genetic diseases with established genetic locus heterogeneity. Sociedade Brasileira de Genética 2021-09-29 /pmc/articles/PMC8485181/ /pubmed/34609444 http://dx.doi.org/10.1590/1678-4685-GMB-2021-0061 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License |
spellingShingle | Human and Medical Genetics Quaio, Caio Robledo D’Angioli Costa Obando, María José Rivadeneira Perazzio, Sandro Felix Dutra, Aurelio Pimenta Chung, Christine Hsiaoyun Moreira, Caroline Monaco Novo, Gil Monteiro Sacramento-Bobotis, Patricia Rossi Penna, Michele Groenner de Souza, Rafaela Rogerio Floriano Cintra, Vivian Pedigone Carnavalli, Juliana Emilia Prior da Silva, Rafael Alves Santos, Monize Nakamoto Provisor Paixão, Daniele Baratela, Wagner Antonio da Rosa Olivati, Caroline Spolador, Gustavo Marquezani Pintao, Maria Carolina Fornari, Alexandre Ricardo dos Santos Burger, Matheus Ramalho, Rodrigo Fernandes Pereira, Otavio Jose Eulalio Ferreira, Elisa Napolitano e Mitne-Neto, Miguel Kim, Chong Ae Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
title | Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
title_full | Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
title_fullStr | Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
title_full_unstemmed | Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
title_short | Exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
title_sort | exome sequencing and targeted gene panels: a simulated comparison of diagnostic yield using data from 158 patients with rare diseases |
topic | Human and Medical Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485181/ https://www.ncbi.nlm.nih.gov/pubmed/34609444 http://dx.doi.org/10.1590/1678-4685-GMB-2021-0061 |
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