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

Flora Tassone12*, Ka Pou Iong1, Tzu-Han Tong1, Joyce Lo1, Louise W Gane2, Elizabeth Berry-Kravis3, Danh Nguyen4, Lisa Y Mu4, Jennifer Laffin5, Don B Bailey6 and Randi J Hagerman27

Author Affiliations

1 Department of Biochemistry and Molecular Medicine, UC Davis, Sacramento, CA 95817, USA

2 MIND Institute, UC Davis Medical Center, Sacramento, CA 95817, USA

3 Department of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA

4 Division of Biostatistics, UC Davis, Davis, CA 95616, USA

5 Department of Pediatrics, University of Wisconsin, Madison, WI 53706, USA

6 RTI International, Research Triangle Park, NC 27709, USA

7 Department of Pediatrics, UC Davis, Sacramento, CA 95817, USA

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Genome Medicine 2012, 4:100  doi:10.1186/gm401

Published: 21 December 2012

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.