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. 2012 Dec 21;4(12):100.
doi: 10.1186/gm401. eCollection 2012.

FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States

Flora Tassone  1 , Ka Pou Iong  2 , Tzu-Han Tong  2 , Joyce Lo  2 , Louise W Gane  3 , Elizabeth Berry-Kravis  4 , Danh Nguyen  5 , Lisa Y Mu  5 , Jennifer Laffin  6 , Don B Bailey  7 , Randi J Hagerman  8
Affiliations

FMR1 CGG allele size and prevalence ascertained through newborn screening in the United States

Flora Tassone et al. Genome Med. .

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.

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Figures

Figure 1
Figure 1
CGG repeat allele size distribution. Histograms display the CGG repeat length observed in the newborn screening by allele category. A) FMR1 alleles in the normal range (<45 CGG repeats, n = 20710 alleles). B) FMR1 alleles in the gray zone range (45-54 CGG repeats, n = 170 alleles). C) FMR1 alleles in the expanded gray zone range (40-54 CGG repeats, n = 614 alleles). D) FMR1 alleles in the premutation range (55-200 CGG repeats, n = 50).
See this image and copyright information in PMC

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