TY - JOUR
T1 - BRCA1/2 mutations and FMR1 alleles are randomly distributed
T2 - A case control study
AU - Dagan, Efrat
AU - Cohen, Yoram
AU - Mory, Adi
AU - Adir, Vardit
AU - Borochowitz, Zvi
AU - Raanani, Hila
AU - Kurolap, Alina
AU - Melikhan-Revzin, Svetlana
AU - Meirow, Dror
AU - Gershoni-Baruch, Ruth
N1 - Funding Information:
We acknowledge the Israeli Jack Craps foundation for funding this research.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - BRCA mutation carriers were reported to display a skewed distribution of FMR1 genotypes, predominantly within the low normal range (CGG repeat number <26). This observation led to the interpretation that BRCA1/2 mutations are embryo-lethal, unless rescued by 'low FMR1 alleles'. We undertook to re-explore the distribution of FMR1 alleles subdivided into low, normal and high (<26, 26-34, and >34 CGG repeats, respectively) subgenotypes, on a cohort of 125 Ashkenazi women, carriers of a BRCA1/2 founder mutation. Ashkenazi healthy females (n=368), tested in the frame of the Israeli screening population program, served as controls. BRCA1/2 carriers and controls demonstrated a comparable and non-skewed FMR1 subgenotype distribution. Taken together, using a homogeneous ethnic group of Ashkenazi BRCA1/2 mutation carriers, we could not confirm the reported association between FMR1 low genotypes and BRCA1/2 mutations. The notion that BRCA1/2 mutations are embryo-lethal unless rescued by the low FMR1 subgenotypes is hereby refuted.
AB - BRCA mutation carriers were reported to display a skewed distribution of FMR1 genotypes, predominantly within the low normal range (CGG repeat number <26). This observation led to the interpretation that BRCA1/2 mutations are embryo-lethal, unless rescued by 'low FMR1 alleles'. We undertook to re-explore the distribution of FMR1 alleles subdivided into low, normal and high (<26, 26-34, and >34 CGG repeats, respectively) subgenotypes, on a cohort of 125 Ashkenazi women, carriers of a BRCA1/2 founder mutation. Ashkenazi healthy females (n=368), tested in the frame of the Israeli screening population program, served as controls. BRCA1/2 carriers and controls demonstrated a comparable and non-skewed FMR1 subgenotype distribution. Taken together, using a homogeneous ethnic group of Ashkenazi BRCA1/2 mutation carriers, we could not confirm the reported association between FMR1 low genotypes and BRCA1/2 mutations. The notion that BRCA1/2 mutations are embryo-lethal unless rescued by the low FMR1 subgenotypes is hereby refuted.
KW - BRCA1/2
KW - CGG repeats
KW - FMR1 subgenotypes
UR - http://www.scopus.com/inward/record.url?scp=84892799692&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2013.281
DO - 10.1038/ejhg.2013.281
M3 - Article
C2 - 24281364
AN - SCOPUS:84892799692
SN - 1018-4813
VL - 22
SP - 277
EP - 279
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 2
ER -