AmplideX FMR1 (IVD CE)

Overview of FMR1 Disorders

Fragile X is a trinucleotide repeat disease caused predominantly by the expansion of CGG sequences in the 5’ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene [1]. The specific number of CGG repeats is associated with a constellation of disorders that can affect patients both young and old [2]. For example, individuals with full mutations (>200 CGG repeats) often present classic fragile X syndrome (FXS), characterized by mental retardation, autistic-like behaviors, and emotional and psychiatric challenges [3]. FXS is the most common known genetic cause of autism and is recommended by recent ACMG practice guidelines as a first tier test for the clinical genetic diagnostic evaluation of autism spectrum disorders [4]. According to the Centers for Disease Control, the incidence of the full mutation is roughly 1 in 4000 males and 1 in 8000 females [5]. Two additional and more recently characterized FMR1 disorders are fragile X-associated tremor/ataxia syndrome (FXTAS), which is primarily associated with parkinsonism and dementia in male pre-mutation carriers over the age of 50, and fragile X primary ovarian insufficiency (FXPOI), a leading cause of ovarian dysfunction in women [6]. Nearly all cases of FXS, FXTAS, and FXPOI are caused by CGG repeat expansion in FMR1. Thus, quantifying the number of CGG repeats is an important goal.
 

FMR1 PCR Research Reagents (IVD CE) Now Available from Asuragen, Inc.

Asuragen has developed a set of  reagents that can be used for human FMR1 molecular analyses. Two PCR formats are supported: 1) a gene-specific FMR1 PCR, and; 2) a CGG repeat primed FMR1 PCR. The repeat primed PCR assay utilizes a novel CGG repeat primer along with gene-specific primers to enable amplification of the entire span of the triplet repeat region, but also each priming event that is possible from all CGG elements present within the repeat segment. Both formats are compatible with capillary electrophoresis. Products include all required amplification reagents and size ladder.

Asuragen also offers research reagents to support FMR1 analyses in non-human animal models, such as mouse. Research applications that require comprehensive FMR1 gene profiling may also be supported.
 

Asuragen currently recommends the following instrumentation for use with these PCR reagents:

Use of instrumentation outside of these recommendations cannot be supported at this time.


POSTERS:

A PCR-only Workflow for FMR1 Analysis that Amplifies Fragile X Full Mutation Alleles, Definitively Resolves Allele Zygosity, and Accurately Assesses Methylation Status

G11: A Rapid PCR Method for the Determination of FMR1 Methylation Status in both Males and Females.

G10: Two Novel PCR Strategies that Amplify and Accurately Report the Full Range of FMR1 Genotypes without the need for Southern Blot.

References

1. Verkerk, A.J., et al., Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 1991. 65(5): p. 905-14.>
2. Hagerman, R.J. and P.J. Hagerman, Testing for fragile X gene mutations throughout the life span. Jama, 2008. 300(20): p. 2419-21.>
3. Hagerman, R.J. and P.J. Hagerman, Fragile X Syndrome: Diagnosis, Treatment, and Research. 3rd ed. 2002, Baltimore: The Johns Hopkins University Press. 3-109.>
4. Schaefer, G.B. and N.J. Mendelsohn, Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med, 2008. 10(4): p. 301-5.>
5. Centers for Disease Control and Prevention. Fragile X Syndrome. http://www.cdc.gov/ncbddd/single_gene/fragilex.htm>
6. Hagerman, R.J. and P.J. Hagerman, The fragile X premutation: into the phenotypic fold. Curr Opin Genet Dev, 2002. 12(3): p. 278-83.>