title: Next-generation sequencing in familial breast cancer patients from Lebanon.
abstract: Familial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16-40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature.
  
  
  
  In the presented study, 45 Lebanese patients with a reported family history of BC were tested using Whole Exome Sequencing (WES) technique followed by Sanger sequencing validation.
  
  
  
  Nineteen pathogenic mutations were identified in this study. These 19 mutations were found in 13 different genes such as: ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53.
  
  
  
  In this first application of WES on BC in Lebanon, we detected six BRCA1 and BRCA2 deleterious mutations in seven patients, with a total prevalence of 15.5%, a figure that is lower than those reported in the Western literature. The p.C44F mutation in the BRCA1 gene appeared twice in this study, suggesting a founder effect. Importantly, the overall mutation prevalence was equal to 40%, justifying the urgent need to deploy WES for the identification of genetic variants responsible for familial BC in the Lebanese population.
authors.affiliation: Unité de Génétique Médicale, Pôle Technologie Santé, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Nadine
authors.initials: N
authors.lastname: Jalkh
authors.affiliation: Unité de Génétique Médicale, Pôle Technologie Santé, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.affiliation: Unité de Génétique Médicale, Pôle Technologie Santé, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Haidar
authors.affiliation: Trad Hospital, Beirut, Lebanon.
authors.forename: Christina
authors.initials: C
authors.lastname: Khater
authors.affiliation: Department of Gynecology and Obstetrics, Hôtel-Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon.
authors.forename: David
authors.initials: D
authors.lastname: Atallah
authors.affiliation: Department of Medical Laboratory Sciences (MLS), Faculty of Allied Health Sciences, Health Sciences Center (HSC), Kuwait University, Safat, Kuwait.|Dasman Diabetes Institute (DDI), P.O Box 1180, Dasman, 15462, Kuwait.
authors.forename: Hamad
authors.initials: H
authors.lastname: Ali
authors.affiliation: Kuwait Medical Genetics Center, Maternity Hospital, Safat, Kuwait.
authors.forename: Makia J
authors.initials: MJ
authors.lastname: Marafie
authors.affiliation: Department of Computing Sciences and Engineering, Kuwait University, P.O. Box 5969, Safat, 13060, Kuwait.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Al-Mulla
authors.affiliation: Dasman Diabetes Institute (DDI), P.O Box 1180, Dasman, 15462, Kuwait. fahd@al-mulla.org.|Health Sciences Center, Faculty of Medicine, Department of Pathology, Kuwait University, P.O.Box 24923, Safat, 13110, Kuwait. fahd@al-mulla.org.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
authors.affiliation: Institut Jerome Lejeune, Paris, France. andre.megarbane@yahoo.fr.
authors.forename: Andre
authors.initials: A
authors.lastname: Megarbane
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007861:Lebanon; D008875:Middle Aged; D009154:Mutation
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein
keywords: BRCA; Breast cancer; Exome; Familial; Germline; Lebanon; Mutation; Next-generation sequencing