The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population
In: ISSN: 1755-8794 ; BMC Medical Genomics ; https://hal-amu.archives-ouvertes.fr/hal-02048914 ; BMC Medical Genomics, 2019, 12 (1), ⟨10.1186/s12920-019-0474-y⟩, 2019
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International audience ; Background:The past few decades have witnessed a tremendous development in the field of genetics. Theimplementation of next generation sequencing (NGS) technologies revolutionized the field of molecular biologyand made the genetic information accessible at a large scale. However, connecting a rare genetic variation to acomplex phenotype remains challenging. Indeed, identifying the cause of a genetic disease requires amultidisciplinary approach, starting with the establishment of a clear phenotype with a detailed family history andending, in some cases, with functional assays that are crucial for the validation of the pathogenicity of a mutation.Methods:Two hundred Lebanese patients, presenting a wide spectrum of genetic disorders (neurodevelopmental,neuromuscular or metabolic disorders, etc.), sporadic or inherited, dominant or recessive, were referred, over thelast three and a half years, to the Medical Genetics Unit (UGM) of Saint Joseph University (USJ). In order to identify the genetic basis of these diseases, Whole Exome Sequencing (WES), followed by a targeted analysis, was performed for each case. In order to improve the genetic diagnostic yield, WES data, generated during the first 2 years of this study, were reanalyzed for all patients who were left undiagnosed at the genetic level. Reanalysis was based on updated bioinformatics tools and novel gene discoveries.Results:Our initial analysis allowed us to identify the specific genetic mutation causing the disease in 49.5% of the cases, in line with other international studies. Repeated WES analysis enabled us to increase the diagnostics yield to 56%.Conclusion:The present article reports the detailed results of both analysis and pinpoints the contribution of WES data reanalysis to an efficient genetic diagnosis. Lessons learned from WES reanalysis and interpretation are also shared.
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The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population
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Autor/in / Beteiligte Person: | Jalkh, Nadine ; Corbani, Sandra ; Haidar, Zahraa ; Hamdan, Nadine ; Farah, Elias ; Abou Ghoch, Joelle ; Ghosn, Rouba ; Salem, Nabiha ; Fawaz, Ali ; Djambas Khayat, Claudia ; Rajab, Mariam ; Mourani, Chebl ; Moukarzel, Adib ; Rassi, Simon ; Gerbaka, Bernard ; Mansour, Hicham ; Baassiri, Malek ; Dagher, Rawane ; Breich, David ; Megarbane, Andre ; Desvignes, Jean-Pierre ; Delague, Valérie ; Mehawej, Cybel ; Chouery, Eliane ; Unité de génétique médicale ; Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Marseille medical genetics - Centre de génétique médicale de Marseille (MMG) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Department, Neuropediatrics ; Lebanese International University (LIU) ; Hôtel-Dieu de France (HDF) ; Université Saint-Joseph de Beyrouth (USJ) ; Makassed General Hospital Beirut, Lebanon ; Saint George Hospital University Medical Center UOB, LIBAN ; University of Balamand Liban (UOB) ; Department of Oncology, Hammoud Hospital University Medical Center ; Notre Dame de Secours University Hospital ; Faculty of Sciences Lebanese University ; Lebanese University Beirut (LU)-Lebanese University Beirut (LU) ; Department of Pediatrics, Chtoura Hospital ; Institut Jérôme Lejeune |
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Zeitschrift: | ISSN: 1755-8794 ; BMC Medical Genomics ; https://hal-amu.archives-ouvertes.fr/hal-02048914 ; BMC Medical Genomics, 2019, 12 (1), ⟨10.1186/s12920-019-0474-y⟩, 2019 |
Veröffentlichung: | HAL CCSD ; BioMed Central, 2019 |
Medientyp: | academicJournal |
DOI: | 10.1186/s12920-019-0474-y |
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