title: AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome.
abstract: OBJECTIVE
  The ability to accurately predict the likelihood of expansion of the CGG repeats in the FMR1 gene to a full mutation is of critical importance for genetic counseling of women who are carriers of premutation alleles (55-200 CGG repeats) and who are weighing the risk of having a child with fragile X syndrome. The presence of AGG interruptions within the CGG repeat tract is thought to decrease the likelihood of expansion to a full mutation during transmission, thereby reducing risk, although their contribution has not been quantified.
  
  
  METHODS
  We retrospectively analyzed 267 premutation alleles for number and position of AGG interruptions, length of pure CGG repeats, and CGG repeat lengths present in the offspring of the maternal transmissions. In addition, we determined the haplotypes of four markers flanking the 5'-UTR locus in the premutation mothers.
  
  
  RESULTS
  We found that the presence of AGG interruptions significantly increased genetic stability, whereas specific haplotypes had a marginal association with transmission instability.
  
  
  CONCLUSIONS
  The presence of AGG interruptions reduced the risk of transmission of a full mutation for all maternal (premutation) repeat lengths below ~100 CGG repeats, with a differential risk (0 vs. 2 AGG) exceeding 60% for alleles in the 70- to 80-CGG repeat range.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California-Davis School of Medicine, Davis, California, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Yrigollen
authors.forename: Blythe
authors.initials: B
authors.lastname: Durbin-Johnson
authors.forename: Louise
authors.initials: L
authors.lastname: Gane
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Randi
authors.initials: R
authors.lastname: Hagerman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hagerman
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
mesh_terms: D000367:Age Factors; D000483:Alleles; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D010375:Pedigree; D019683:Penetrance; D012306:Risk; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human