title: X-inactivation in the clinical phenotype of fragile X premutation carrier sisters.
abstract: OBJECTIVE
  The purpose of this study is to describe a case series of 4 sisters with discordant clinical phenotypes associated with fragile X-associated tremor/ataxia syndrome (FXTAS) that may be explained by varying CGG repeat sizes and activation ratios (ARs) (the ratio of cells carrying the normal fragile X mental retardation 1 [FMR1] allele on the active X chromosome).
  
  
  METHODS
  Four sisters with premutation size FMR1 gene repeats underwent detailed clinical characterization. CGG repeat length was determined by PCR, and AR was determined using a newly developed commercial methylation PCR assay and was compared with the results from Southern blot with densitometric image analysis.
  
  
  RESULTS
  Sister 1 had the largest CGG expansion (82) and the lowest AR (12%), with the most severe clinical presentation. Sister 2 had a lower CGG expansion (70) and an AR of 10% but had a milder clinical presentation.Sister 3 had a similar CGG expansion (79) but a slightly higher AR of 15% and less neurologic involvement. Sister 4 had a similar CGG expansion size of 80 but had the largest AR (40%) and was the only sister not to be affected by FXTAS or have any neurologic signs on examination.
  
  
  CONCLUSIONS
  These results suggest that premutation carrier women who have higher ARs may be less likely to show manifestations of FXTAS. If larger studies show similar patterns, AR data could potentially be beneficial to supplement CGG repeat size when counseling premutation carrier women in the clinic.
authors.affiliation: Department of Neurological Sciences (D.A.H., E.B.-K.), Department of Anatomy and Cell Biology (E.E.R.-D., J.A.O.), Department of Biochemistry (L.Z., E.B.-K.), and Department of Pediatrics (E.B.-K.), Rush University, Chicago, IL; and Asuragen, Inc. (A.G.H.), Austin, TX.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hall
authors.affiliation: Department of Neurological Sciences (D.A.H., E.B.-K.), Department of Anatomy and Cell Biology (E.E.R.-D., J.A.O.), Department of Biochemistry (L.Z., E.B.-K.), and Department of Pediatrics (E.B.-K.), Rush University, Chicago, IL; and Asuragen, Inc. (A.G.H.), Austin, TX.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Robertson-Dick
authors.affiliation: Department of Neurological Sciences (D.A.H., E.B.-K.), Department of Anatomy and Cell Biology (E.E.R.-D., J.A.O.), Department of Biochemistry (L.Z., E.B.-K.), and Department of Pediatrics (E.B.-K.), Rush University, Chicago, IL; and Asuragen, Inc. (A.G.H.), Austin, TX.
authors.forename: Joan A
authors.initials: JA
authors.lastname: O'Keefe
authors.affiliation: Department of Neurological Sciences (D.A.H., E.B.-K.), Department of Anatomy and Cell Biology (E.E.R.-D., J.A.O.), Department of Biochemistry (L.Z., E.B.-K.), and Department of Pediatrics (E.B.-K.), Rush University, Chicago, IL; and Asuragen, Inc. (A.G.H.), Austin, TX.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hadd
authors.affiliation: Department of Neurological Sciences (D.A.H., E.B.-K.), Department of Anatomy and Cell Biology (E.E.R.-D., J.A.O.), Department of Biochemistry (L.Z., E.B.-K.), and Department of Pediatrics (E.B.-K.), Rush University, Chicago, IL; and Asuragen, Inc. (A.G.H.), Austin, TX.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurological Sciences (D.A.H., E.B.-K.), Department of Anatomy and Cell Biology (E.E.R.-D., J.A.O.), Department of Biochemistry (L.Z., E.B.-K.), and Department of Pediatrics (E.B.-K.), Rush University, Chicago, IL; and Asuragen, Inc. (A.G.H.), Austin, TX.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Berry-Kravis