title: FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States.
abstract: BACKGROUND
  Population screening for FMR1 mutations has been a topic of considerable discussion since the FMR1 gene was identified in 1991. Advances in understanding the molecular basis of fragile X syndrome (FXS) and in genetic testing methods have led to new, less expensive methodology to use for large screening endeavors. A core criterion for newborn screening is an accurate understanding of the public health burden of a disease, considering both disease severity and prevalence rate. This article addresses this need by reporting prevalence rates observed in a pilot newborn screening study for FXS in the US.
  
  
  METHODS
  Blood spot screening of 14,207 newborns (7,312 males and 6,895 females) was conducted in three birthing hospitals across the United States beginning in November 2008, using a PCR-based approach.
  
  
  RESULTS
  The prevalence of gray zone alleles was 1:66 females and 1:112 males, while the prevalence of a premutation was 1:209 females and 1:430 males. Differences in prevalence rates were observed among the various ethnic groups; specifically higher frequency for gray zone alleles in males was observed in the White group compared to the Hispanic and African-American groups. One full mutation male was identified (>200 CGG repeats).
  
  
  CONCLUSIONS
  The presented pilot study shows that newborn screening in fragile X is technically feasible and provides overall prevalence of the premutation and gray zone alleles in the USA, suggesting that the prevalence of the premutation, particularly in males, is higher than has been previously reported.
authors.affiliation: Department of Biochemistry and Molecular Medicine, UC Davis, Sacramento, CA 95817, USA ; MIND Institute, UC Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
authors.affiliation: Department of Biochemistry and Molecular Medicine, UC Davis, Sacramento, CA 95817, USA.
authors.forename: Ka Pou
authors.initials: KP
authors.lastname: Iong
authors.affiliation: Department of Biochemistry and Molecular Medicine, UC Davis, Sacramento, CA 95817, USA.
authors.forename: Tzu-Han
authors.initials: TH
authors.lastname: Tong
authors.affiliation: Department of Biochemistry and Molecular Medicine, UC Davis, Sacramento, CA 95817, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Lo
authors.affiliation: MIND Institute, UC Davis Medical Center, Sacramento, CA 95817, USA.
authors.forename: Louise W
authors.initials: LW
authors.lastname: Gane
authors.affiliation: Department of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Berry-Kravis
authors.affiliation: Division of Biostatistics, UC Davis, Davis, CA 95616, USA.
authors.forename: Danh
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Division of Biostatistics, UC Davis, Davis, CA 95616, USA.
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Mu
authors.affiliation: Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Laffin
authors.affiliation: RTI International, Research Triangle Park, NC 27709, USA.
authors.forename: Don B
authors.initials: DB
authors.lastname: Bailey
authors.affiliation: MIND Institute, UC Davis Medical Center, Sacramento, CA 95817, USA ; Department of Pediatrics, UC Davis, Sacramento, CA 95817, USA.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman