Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Genética 2021
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
_version_ 1784577484239405056
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
work_keys_str_mv AT quaiocaiorobledodangiolicosta exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT obandomariajoserivadeneira exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT perazziosandrofelix exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT dutraaureliopimenta exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT chungchristinehsiaoyun exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT moreiracarolinemonaco exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT novogilmonteiro exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT sacramentobobotispatriciarossi exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT pennamichelegroenner exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT desouzarafaelarogeriofloriano exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT cintravivianpedigone exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT carnavallijulianaemiliaprior exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT dasilvarafaelalves exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT santosmonizenakamotoprovisor exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT paixaodaniele exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT baratelawagnerantoniodarosa exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT olivaticaroline exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT spoladorgustavomarquezani exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT pintaomariacarolina exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT fornarialexandrericardodossantos exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT burgermatheus exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT ramalhorodrigofernandes exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT pereiraotaviojoseeulalio exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT ferreiraelisanapolitanoe exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT mitnenetomiguel exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases
AT kimchongae exomesequencingandtargetedgenepanelsasimulatedcomparisonofdiagnosticyieldusingdatafrom158patientswithrarediseases