Increased diagnostic and new genes ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing
Auteur(s) :
Bruel, Ange-Line [Auteur]
Nambot, Sophie [Auteur]
Quere, Virginie [Auteur]
Vitobello, Antonio [Auteur]
Thevenon, Julien [Auteur]
Assoum, Mirna [Auteur]
Moutton, Sebastien [Auteur]
Houcinat, Nada [Auteur]
Lehalle, Daphne [Auteur]
Jean-Marcais, Nolwenn [Auteur]
Chevarin, Martin [Auteur]
Jouan, Thibaud [Auteur]
Poe, Charlotte [Auteur]
Callier, Patrick [Auteur]
Tisserand, Emilie [Auteur]
Philippe, Christophe [Auteur]
Tran Mau-Them, Frederic [Auteur]
Duffourd, Yannis [Auteur]
Faivre, Laurence [Auteur]
Thauvin-Robinet, Christel [Auteur]
Nambot, Sophie [Auteur]
Quere, Virginie [Auteur]
Vitobello, Antonio [Auteur]
Thevenon, Julien [Auteur]
Assoum, Mirna [Auteur]
Moutton, Sebastien [Auteur]
Houcinat, Nada [Auteur]
Lehalle, Daphne [Auteur]
Jean-Marcais, Nolwenn [Auteur]
Chevarin, Martin [Auteur]
Jouan, Thibaud [Auteur]
Poe, Charlotte [Auteur]
Callier, Patrick [Auteur]
Tisserand, Emilie [Auteur]
Philippe, Christophe [Auteur]
Tran Mau-Them, Frederic [Auteur]
Duffourd, Yannis [Auteur]
Faivre, Laurence [Auteur]
Thauvin-Robinet, Christel [Auteur]
Titre de la revue :
European journal of human genetics . EJHG
Nom court de la revue :
Eur. J. Hum. Genet.
Date de publication :
2019-06-23
ISSN :
1476-5438
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
In clinical exome sequencing (cES), the American College of Medical Genetics and Genomics recommends limiting variant interpretation to established human-disease genes. The diagnostic yield of cES in intellectual disability ...
Lire la suite >In clinical exome sequencing (cES), the American College of Medical Genetics and Genomics recommends limiting variant interpretation to established human-disease genes. The diagnostic yield of cES in intellectual disability and/or multiple congenital anomalies (ID/MCA) is currently about 30%. Though the results may seem acceptable for rare diseases, they mean that 70% of affected individuals remain genetically undiagnosed. Further analysis extended to all mutated genes in a research environment is a valuable strategy for improving diagnostic yields. This study presents the results of systematic research reanalysis of negative cES in a cohort of 313 individuals with ID/MCA. We identified 17 new genes not related to human disease, implicated 22 non-OMIM disease-causing genes recently or previously rarely related to disease, and described 1 new phenotype associated with a known gene. Twenty-six candidate genes were identified and are waiting for future recurrence. Overall, we diagnose 15% of the individuals with initial negative cES, increasing the diagnostic yield from 30% to more than 40% (or 46% if strong candidate genes are considered). This study demonstrates the power of such extended research reanalysis to increase scientific knowledge of rare diseases. These novel findings can then be applied in the field of diagnostics.Lire moins >
Lire la suite >In clinical exome sequencing (cES), the American College of Medical Genetics and Genomics recommends limiting variant interpretation to established human-disease genes. The diagnostic yield of cES in intellectual disability and/or multiple congenital anomalies (ID/MCA) is currently about 30%. Though the results may seem acceptable for rare diseases, they mean that 70% of affected individuals remain genetically undiagnosed. Further analysis extended to all mutated genes in a research environment is a valuable strategy for improving diagnostic yields. This study presents the results of systematic research reanalysis of negative cES in a cohort of 313 individuals with ID/MCA. We identified 17 new genes not related to human disease, implicated 22 non-OMIM disease-causing genes recently or previously rarely related to disease, and described 1 new phenotype associated with a known gene. Twenty-six candidate genes were identified and are waiting for future recurrence. Overall, we diagnose 15% of the individuals with initial negative cES, increasing the diagnostic yield from 30% to more than 40% (or 46% if strong candidate genes are considered). This study demonstrates the power of such extended research reanalysis to increase scientific knowledge of rare diseases. These novel findings can then be applied in the field of diagnostics.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Date de dépôt :
2021-09-02T07:01:26Z