Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Jun;16(6):666-72.
doi: 10.1038/ejhg.2008.61. Epub 2008 Apr 9.

Fragile X syndrome

Kathryn B Garber  1 , Jeannie Visootsak, Stephen T Warren
Affiliations
Review

Fragile X syndrome

Kathryn B Garber et al. Eur J Hum Genet. 2008 Jun.

Abstract

Fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is associated with intellectual and emotional disabilities ranging from learning problems to mental retardation, and mood instability to autism. It is most often caused by the transcriptional silencing of the FMR1 gene, due to an expansion of a CGG repeat found in the 5'-untranslated region. The FMR1 gene product, FMRP, is a selective RNA-binding protein that negatively regulates local protein synthesis in neuronal dendrites. In its absence, the transcripts normally regulated by FMRP are over translated. The resulting over abundance of certain proteins results in reduced synaptic strength due to AMPA receptor trafficking abnormalities that lead, at least in part, to the fragile X phenotype.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Four allelic classes of the FMR1 gene in humans. For each allele, the size of the CGG repeat in the 5′-UTR of FMR1 is indicated in blue at the left of the gene schematic. The level of transcription is indicated by the width of the arrow beneath each allele class. Increased transcription is associated with premutation alleles, whereas full mutations are hypermethylated, as indicated by the red hashmarks, and transcriptionally silent. Despite the ACMG definition, the smallest premutation allele known to expand to the full mutation in a single generation had 59 repeats.
Figure 2
Figure 2
Facial features of fragile X syndrome. As illustrated by the photographs of four children with FXS, the facies associated with this syndrome are subtle. They can include a long, thin face, and prominent ears that often project away from the head, and a prominent forehead.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Crawford DC, Acuna JM, Sherman SL. FMR1 and the fragile X syndrome: human genome epidemiology review. Genet Med. 2001;3:359–371. - PMC - PubMed
    1. Sherman SL, Jacobs PA, Morton NE, et al. Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet. 1985;69:289–299. - PubMed
    1. Maes B, Fryns JP, Ghesquiere P, Borghgraef M. Phenotypic checklist to screen for fragile X syndrome in people with mental retardation. Ment Retard. 2000;38:207–215. - PubMed
    1. Merenstein SA, Sobesky WE, Taylor AK, Riddle JE, Tran HX, Hagerman RJ. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet. 1996;64:388–394. - PubMed
    1. Kemper MB, Hagerman RJ, Altshul-Stark D. Cognitive profiles of boys with the fragile X syndrome. Am J Med Genet. 1988;30:191–200. - PubMed

MeSH terms

Substances