Fragile X AGG analysis provides new risk predictions for 45-69 repeat alleles

Sarah L. Nolin, Sachin Sah, Anne Glicksman, Stephanie L. Sherman, Emily Allen, Elizabeth Berry-Kravis, Flora Tassone, Carolyn Yrigollen, Amy Cronister, Marcia Jodah, Nicole Ersalesi, Carl Dobkin, W. Ted Brown, Raghav Shroff, Gary J. Latham, Andrew G. Hadd

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


We investigated the effect of AGG interruptions on fragile X repeat instability upon transmission of fragile X intermediate and small premutation alleles with 45-69 CGG repeats. The FMR1 repeat structure was determined for 375 mothers, 48 fathers, and 538 offspring (457 maternal and 81 paternal transmissions) using a novel PCR assay to determine repeat length and AGG interruptions. The number of AGG interruptions and the length of uninterrupted CGG repeats at the 3′ end were correlated with repeat instability on transmission. Maternal alleles with no AGGs conferred the greatest risk for unstable transmissions. All nine full mutation expansions were inherited from maternal alleles with no AGGs. Furthermore, the magnitude of repeat expansion was larger for alleles lacking AGG interruptions. Transmissions from paternal alleles with no AGGs also exhibited greater instability than those with one or more AGGs. Our results demonstrate that characterization of the AGG structure within the FMR1 repeat allows more accurate risk estimates of repeat instability and expansion to full mutations for intermediate and small premutation alleles.

Original languageEnglish (US)
Pages (from-to)771-778
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Issue number4
StatePublished - Apr 2013


  • FMR1
  • Fragile X
  • Trinucleotide repeat instability

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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