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BMC Med Genomics. 2019 Jan 21;12(1):11. doi: 10.1186/s12920-019-0474-y.

The added value of WES reanalysis in the field of genetic diagnosis: lessons learned from 200 exomes in the Lebanese population.

Author information

1
Unité de Génétique Médicale, Faculté de Médecine, Campus De l'innovation et du sport, Université Saint-Joseph, rue de Damas, Beirut, Lebanon.
2
Service de technologie de l'information, Saint Joseph University, Beirut, Lebanon.
3
Neuropediatrics Department, Lebanese University, Beirut, Lebanon.
4
Division of Pediatrics, Hotel Dieu de France Hospital, Beirut, Lebanon.
5
Department of Pediatrics Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
6
Department of Pediatrics, Makassed General Hospital, Beirut, Lebanon.
7
Department of Otolaryngology-Head and Neck Surgery, Hotel Dieu de France Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
8
Pediatric Neurometabolic Unit, Saint George University Medical Center, Beyrouth, Lebanon.
9
Department of Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon.
10
Department of Pediatrics, Notre Dame De Secours University Hospital, Byblos, Lebanon.
11
Department of Pediatrics, Chtoura Hospital, Chtoura, Lebanon.
12
Unité de Génétique Médicale, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
13
Institut Jérôme Lejeune, Paris, France.
14
Aix Marseille Univ, Inserm, MMG, U 1251, Marseille, France.
15
Unité de Génétique Médicale, Faculté de Médecine, Campus De l'innovation et du sport, Université Saint-Joseph, rue de Damas, Beirut, Lebanon. eliane.chouery@usj.edu.lb.

Abstract

BACKGROUND:

The past few decades have witnessed a tremendous development in the field of genetics. The implementation of next generation sequencing (NGS) technologies revolutionized the field of molecular biology and made the genetic information accessible at a large scale. However, connecting a rare genetic variation to a complex phenotype remains challenging. Indeed, identifying the cause of a genetic disease requires a multidisciplinary approach, starting with the establishment of a clear phenotype with a detailed family history and ending, 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 the last 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.

KEYWORDS:

Exome; Genetic diagnostics; Genetic heterogeneity; High throughput sequencing; Lebanon; Mutations; NGS

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