title: Ethnic effect on FMR1 carrier rate and AGG repeat interruptions among Ashkenazi women.
abstract: OBJECTIVE
  Fragile X syndrome, a common cause of intellectual disability, is usually caused by CGG trinucleotide expansion in the FMR1 gene. CGG repeat size correlates with expansion risk. Premutation alleles (55-200 repeats) may expand to full mutations in female meiosis. Interspersed AGG repeats decrease allele instability and expansion risk. The carrier rate and stability of FMR1 alleles were evaluated in large cohorts of Ashkenazi and non-Ashkenazi women.
  
  
  METHODS
  A total of 4,344 Ashkenazi and 4,985 non-Ashkenazi cases were analyzed using Southern blotting and polymerase chain reaction between 2004 and 2011. In addition, AGG interruptions were evaluated in 326 Ashkenazi and 298 non-Ashkenazi women who were recruited during 2011.
  
  
  RESULTS
  Both groups had major peaks of 30 and 29 repeats. Ashkenazi women had a higher frequency of 30 repeats and a lower frequency of other peaks (P < 0.0001). A higher rate of premutations in the 55-59 repeats range (1:114 vs. 1:277) was detected among the Ashkenazi women. Loss of AGG interruptions (<2) was significantly less common among Ashkenazi women (9 vs. 19.5% for non-Ashkenazi women, P = 0.0002).
  
  
  CONCLUSIONS
  Ashkenazi women have a high fragile X syndrome carrier rate and mostly lower-range premutations, and carry a low risk for expansion to a full mutation. Normal-sized alleles in Ashkenazi women have higher average number of AGG interruptions that may increase stability. These factors may decrease the risk for fragile X syndrome offspring among Ashkenazi women.
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Karin
authors.initials: K
authors.lastname: Weiss
authors.affiliation: 1] Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel [2] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Idit
authors.initials: I
authors.lastname: Kaplan Ber
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Tova
authors.initials: T
authors.lastname: Naiman
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Shomrat
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Bardugu
authors.affiliation: 1] Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel [2] Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yaron
authors.affiliation: Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Shachar
mesh_terms: D000483:Alleles; D005006:Ethnicity / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000208:ethnology* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D008540:Meiosis; D009154:Mutation; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human