Ethnic effect on FMR1 carrier rate and AGG repeat interruptions among Ashkenazi women

Purpose: 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 (