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 (RUO)* Now Available from Asuragen, Inc.
Asuragen has developed a set of RUO 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:
- ABI 9700 Thermocycler, ABI Veriti, or MJ Research PTC-200 thermal cycler>
- ABI 3130xl or ABI 3730 Capillary Electrophoresis with POP-7 liquid polymer; 36 cm
capillary preferred>
Use of instrumentation outside of these recommendations cannot be supported at this
time.
For more information, please inquire to fragilexbd@asuragen.com.
*Research Use Only. Not intended for use in diagnostic procedures.
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.>