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Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet–Biedl and Usher Syndromes

Department of Biological and Environmental Sciences, Faculty of Science, Beirut Arab University, Debbieh 1107 2809, Lebanon
Rammal Hassan Rammal Research Laboratory, Physiotoxicity (PhyTox), Faculty of Sciences, Lebanese University, Nabatieh 1700, Lebanon
Retinal Service, Beirut Eye & ENT Specialist Hospital, Beirut 1106, Lebanon
ER045, PRASE, DSST, Lebanese University, Beirut 1700, Lebanon
Biology Department, Faculty of Sciences-I, Lebanese University, Beirut 1700, Lebanon
Sorbonne Université, INSERM, CNRS, Institut de la Vision, 75012 Paris, France
CHNO des Quinze-Vingts, INSERM-DGOS CIC1423, 75012 Paris, France
University College London Institute of Ophthalmology, London EC1V 9EL, UK
Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut 1107 2809, Lebanon
Author to whom correspondence should be addressed.
Equal contributions.
Genes 2019, 10(12), 1047;
Received: 28 October 2019 / Revised: 10 December 2019 / Accepted: 10 December 2019 / Published: 16 December 2019
(This article belongs to the Special Issue Molecular Genetics of Retinal Dystrophies)
Aim: To identify disease-causing mutations in four Lebanese families: three families with Bardet–Biedl and one family with Usher syndrome (BBS and USH respectively), using next generation sequencing (NGS). Methods: We applied targeted NGS in two families and whole exome sequencing (WES) in two other families. Pathogenicity of candidate mutations was evaluated according to frequency, conservation, in silico prediction tools, segregation with disease, and compatibility with inheritance pattern. The presence of pathogenic variants was confirmed via Sanger sequencing followed by segregation analysis. Results: Most likely disease-causing mutations were identified in all included patients. In BBS patients, we found (M1): c.2258A > T, p. (Glu753Val) in BBS9, (M2): c.68T > C; p. (Leu23Pro) in ARL6, (M3): c.265_266delTT; p. (Leu89Valfs*11) and (M4): c.880T > G; p. (Tyr294Asp) in BBS12. A previously known variant (M5): c.551A > G; p. (Asp184Ser) was also detected in BBS5. In the USH patient, we found (M6): c.188A > C, p. (Tyr63Ser) in CLRN1. M2, M3, M4, and M6 were novel. All of the candidate mutations were shown to be likely disease-causing through our bioinformatic analysis. They also segregated with the corresponding phenotype in available family members. Conclusion: This study expanded the mutational spectrum and showed the genetic diversity of BBS and USH. It also spotlighted the efficiency of NGS techniques in revealing mutations underlying clinically and genetically heterogeneous disorders. View Full-Text
Keywords: inherited retinal diseases; next generation sequencing; mutations; Sanger sequencing inherited retinal diseases; next generation sequencing; mutations; Sanger sequencing
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Jaffal, L.; Joumaa, W.H.; Assi, A.; Helou, C.; Cherfan, G.; Zibara, K.; Audo, I.; Zeitz, C.; El Shamieh, S. Next Generation Sequencing Identifies Five Novel Mutations in Lebanese Patients with Bardet–Biedl and Usher Syndromes. Genes 2019, 10, 1047.

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