title: Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers.
abstract: OBJECTIVE
  Fragile X CGG repeat alleles often contain one or more AGG interruptions that influence allele stability and risk of a full mutation transmission from parent to child. We have examined transmissions of maternal and paternal alleles with 45-90 repeats to quantify the effect of AGG interruptions on fragile X repeat instability.
  
  
  METHODS
  A novel FMR1 polymerase chain reaction assay was used to determine CGG repeat length and AGG interruptions for 1,040 alleles from 705 families.
  
  
  RESULTS
  We grouped transmissions into nine categories of five repeats by parental size and found that in every size category, alleles with no AGGs had the greatest risk for instability. For maternal alleles <75 repeats, 89% (24/27) that expanded to a full mutation had no AGGs. Two contractions in maternal transmission were accompanied by loss of AGGs, suggesting a mechanism for generating alleles that lack AGG interruptions. Maternal age was examined as a factor in full mutation expansions using prenatal samples to minimize ascertainment bias, and a possible effect was observed though it was not statistically significant (P = 0.06).
  
  
  CONCLUSIONS
  These results strengthen the association of AGG repeats with CGG repeat stability and provide more accurate risk estimates of full mutation expansions for women with 45-90 repeat alleles.
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Nolin
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Glicksman
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ersalesi
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Dobkin
authors.affiliation: Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
authors.affiliation: Asuragen Inc., Austin, Texas, USA.
authors.forename: Ru
authors.initials: R
authors.lastname: Cao
authors.affiliation: Asuragen Inc., Austin, Texas, USA.
authors.forename: Eliot
authors.initials: E
authors.lastname: Blatt
authors.affiliation: Asuragen Inc., Austin, Texas, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Sah
authors.affiliation: Asuragen Inc., Austin, Texas, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Latham
authors.affiliation: Asuragen Inc., Austin, Texas, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hadd
mesh_terms: D000367:Age Factors; D000483:Alleles; D020132:Anticipation, Genetic; D005190:Family; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics*; D005820:Genetic Testing; D042822:Genomic Instability; D006579:Heterozygote; D006801:Humans; D008297:Male; D008403:Mass Screening; D009030:Mosaicism; D009154:Mutation; D016133:Polymerase Chain Reaction; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1