TY - JOUR
T1 - The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries
AU - Laitman, Yael
AU - Friebel, Tara M.
AU - Yannoukakos, Drakoulis
AU - Fostira, Florentia
AU - Konstantopoulou, Irene
AU - Figlioli, Gisella
AU - Bonanni, Bernardo
AU - Manoukian, Siranoush
AU - Zuradelli, Monica
AU - Tondini, Carlo
AU - Pasini, Barbara
AU - Peterlongo, Paolo
AU - Plaseska-Karanfilska, Dijana
AU - Jakimovska, Milena
AU - Majidzadeh, Keivan
AU - Zarinfam, Shiva
AU - Loizidou, Maria A.
AU - Hadjisavvas, Andreas
AU - Michailidou, Kyriaki
AU - Kyriacou, Kyriacos
AU - Behar, Doron M.
AU - Molho, Rinat Bernstein
AU - Ganz, Patricia
AU - James, Paul
AU - Parsons, Michael T.
AU - Sallam, Aminah
AU - Olopade, Olufunmilayo I.
AU - Seth, Arun
AU - Chenevix - Trench, Georgia
AU - Leslie, Goska
AU - McGuffog, Lesley
AU - Marafie, Makia J.
AU - Megarbane, Andre
AU - Al-Mulla, Fahd
AU - Rebbeck, Timothy R.
AU - Friedman, Eitan
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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in PUBMED, EMBASE, BIC, and CIMBA was carried out combined with outreach to researchers from the relevant countries for unpublished data.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.
AB - 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.
KW - BRCA1 BRCA2 mutational spectrum
KW - first pass genotyping
KW - inherited breast cancer
KW - Middle East
KW - North Africa
KW - underserved populations
UR - http://www.scopus.com/inward/record.url?scp=85073667975&partnerID=8YFLogxK
U2 - 10.1002/humu.23842
DO - 10.1002/humu.23842
M3 - Article
C2 - 31209999
AN - SCOPUS:85073667975
VL - 40
SP - e1-e23
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 11
ER -