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The Spectrum of Brca1 and Brca2 Pathogenic Sequence Variants in Middle Eastern, North African, and South European Countries Publisher Pubmed



Laitman Y1 ; Friebel TM2 ; Yannoukakos D3 ; Fostira F3 ; Konstantopoulou I3 ; Figlioli G4 ; Bonanni B5 ; Manoukian S6 ; Zuradelli M7 ; Tondini C8 ; Pasini B9 ; Peterlongo P4 ; Plaseskakaranfilska D10 ; Jakimovska M10 Show All Authors
Authors
  1. Laitman Y1
  2. Friebel TM2
  3. Yannoukakos D3
  4. Fostira F3
  5. Konstantopoulou I3
  6. Figlioli G4
  7. Bonanni B5
  8. Manoukian S6
  9. Zuradelli M7
  10. Tondini C8
  11. Pasini B9
  12. Peterlongo P4
  13. Plaseskakaranfilska D10
  14. Jakimovska M10
  15. Majidzadeh K11
  16. Zarinfam S11
  17. Loizidou MA12
  18. Hadjisavvas A12
  19. Michailidou K12
  20. Kyriacou K12
  21. Behar DM13
  22. Molho RB14, 15
  23. Ganz P16
  24. James P17
  25. Parsons MT18
  26. Sallam A19
  27. Olopade OI19
  28. Seth A20
  29. Chenevix Trench G18
  30. Leslie G21
  31. Mcguffog L21
  32. Marafie MJ22
  33. Megarbane A23
  34. Almulla F24
  35. Rebbeck TR2, 25
  36. Friedman E1, 15
Show Affiliations
Authors Affiliations
  1. 1. The Susanne Levy Gertner Oncogenetics Unit, The Institute of Human Genetics, Sheba Medical Center, Tel-Hashomer, Israel
  2. 2. Dana-Farber Cancer Institute, Boston, MA, United States
  3. 3. Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research Demokritos, Athens, Greece
  4. 4. Genome Diagnostics Program, IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy
  5. 5. Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy
  6. 6. Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy
  7. 7. Medical Oncology and Hematology Department, Humanitas Cancer Center, Milan, Italy
  8. 8. Department of Medical Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy
  9. 9. Department of Medical Sciences, University of Turin, Turin, Italy
  10. 10. Macedonian Academy of Sciences and Arts Research Centre for Genetic Engineering and Biotechnology, Skopje, North Macedonia
  11. 11. Department of Genetics, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
  12. 12. Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, The Cyprus School of Molecular Medicine, Nicosia, Cyprus
  13. 13. Igentify, Tirat Hacrmel, Israel
  14. 14. The Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Israel
  15. 15. The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  16. 16. Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Centre, UCLA, Los Angeles, CA, United States
  17. 17. Parkville Familial Cancer Peter MacCallum Cancer Center, Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia
  18. 18. Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Queensland Institute of Medical Research, Brisbane, Australia
  19. 19. Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL, United States
  20. 20. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Canada
  21. 21. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
  22. 22. Kuwait Medical Genetics Center, Maternity Hospital, Kuwait
  23. 23. Institut Jerome Lejeune, Paris, France
  24. 24. Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait City, Kuwait
  25. 25. Harvard T.H. Chan School of Public Health, Boston, MA, United States

Source: Human Mutation Published:2019


Abstract

BRCA1 BRCA2 mutational spectrum in the Middle East, North Africa, and Southern Europe is not well characterized. The unique history and cultural practices characterizing these regions, often involving consanguinity and inbreeding, plausibly led to the accumulation of population-specific founder pathogenic sequence variants (PSVs). To determine recurring BRCA PSVs in these locales, a search in PUBMED, EMBASE, BIC, and CIMBA was carried out combined with outreach to researchers from the relevant countries for unpublished data. We identified 232 PSVs in BRCA1 and 239 in BRCA2 in 25 of 33 countries surveyed. Common PSVs that were detected in four or more countries were c.5266dup (p.Gln1756Profs), c.181T>G (p.Cys61Gly), c.68_69del (p.Glu23Valfs), c.5030_5033del (p.Thr1677Ilefs), c.4327C>T (p.Arg1443Ter), c.5251C>T (p.Arg1751Ter), c.1016dup (p.Val340Glyfs), c.3700_3704del (p.Val1234Glnfs), c.4065_4068del (p.Asn1355Lysfs), c.1504_1508del (p.Leu502Alafs), c.843_846del (p.Ser282Tyrfs), c.798_799del (p.Ser267Lysfs), and c.3607C>T (p.Arg1203Ter) in BRCA1 and c.2808_2811del (p.Ala938Profs), c.5722_5723del (p.Leu1908Argfs), c.9097dup (p.Thr3033Asnfs), c.1310_1313del (p. p.Lys437Ilefs), and c.5946del (p.Ser1982Argfs) for BRCA2. Notably, some mutations (e.g., p.Asn257Lysfs (c.771_775del)) were observed in unrelated populations. Thus, seemingly genotyping recurring BRCA PSVs in specific populations may provide first pass BRCA genotyping platform. © 2019 Wiley Periodicals, Inc.