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. 2009 Jul;11(4):324-9.
doi: 10.2353/jmoldx.2009.080173. Epub 2009 May 21.

Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population

Isabel Fernandez-Carvajal  1 , Paulina Walichiewicz, Xie Xiaosen, Ruiqin Pan, Paul J Hagerman, Flora Tassone
Affiliations

Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population

Isabel Fernandez-Carvajal et al. J Mol Diagn. 2009 Jul.

Abstract

Fragile X syndrome, which is caused by expanded CGG repeats of the FMR1 gene, is associated with a broad spectrum of clinical involvement and is the most common inherited form of intellectual disability. Early diagnosis and intervention are likely to lead to improved outcome for children with fragile X syndrome, but such strategies require better estimates of the frequencies of expanded alleles of the FMR1 gene. In this study, we report the results of a newborn screening study of 5267 male blood spots collected from the Northwest region of Spain as part of the national newborn screening program. The blood spots were screened using a rapid polymerase chain reaction-based method that is capable of identifying the presence of all expanded alleles for both males and females. The screened samples included 199 gray zone alleles, 21 premutation alleles, and two full mutation alleles (1 in 2633). The frequency of premutation alleles was three times higher (1 in 251) than the quoted value of 1 in 813 from a Canadian population and is fully consistent with the results of large-scale Israeli screening studies. Our results demonstrate that newborn screening for the presence of expanded FMR1 alleles is an effective means for defining the distribution of expanded FMR1 alleles in newborn populations; as such, this method is suitable for large-scale newborn screening.

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Figures

Figure 1
Figure 1
Example of sizing of FMR1 alleles obtained from blood spots included in this study. Premutation alleles: lanes 2, 3, 4, 5, 8, 9, 11 and 13. Gray zone alleles: lanes 7, 10, and 12; normal alleles: lanes 1, 6, and 14. Lane 15: female control (30, 54 CGG size determined by sequencing). A DNA size marker 100 bp, 3 kb (Qiaxcel) was used to size the different alleles.
Figure 2
Figure 2
Detection of large CGG repeat expansions using a CGG-targeting PCR primer. Lanes 1 and 4, the two full-mutation alleles identified in this study; lanes 2 and 3, normal alleles identified in this study; lanes 5 and 6, normal and full mutation controls; lane 7, negative control.
Figure 3
Figure 3
Distribution of the sizes of the 5233 FMR1 alleles analyzed in the current study.
See this image and copyright information in PMC

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Uncited reference

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