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Fragile X-Linked Mental Retardation

Biochemistry

  1. Ilse Gantois1,
  2. R. Frank Kooy1,
  3. Ben A. Oostra2

Published Online: 15 SEP 2006

DOI: 10.1002/3527600906.mcb.200300051

Reviews in Cell Biology and Molecular Medicine

Reviews in Cell Biology and Molecular Medicine

How to Cite

Gantois, I., Kooy, R. F. and Oostra, B. A. 2006. Fragile X-Linked Mental Retardation. Reviews in Cell Biology and Molecular Medicine. .

Author Information

  1. 1

    University of Antwerp, Antwerp, Belgium

  2. 2

    Department of Clinical Genetics, Rotterdam, Erasmus MC, The Netherlands

Publication History

  1. Published Online: 15 SEP 2006

Abstract

Fragile X syndrome is the most common form of inherited mental retardation. The disease is caused by methylation-induced transcriptional silencing of the fragile X mental retardation 1 gene (FMR1) as a result of the expansion of a CGG repeat in the 5′ UTR of the gene. This leads to the loss of fragile X mental retardation protein product (FMRP). FMRP is an RNA-binding protein that associates with translating polyribosomes as part of a large messenger ribonucleoprotein (mRNP) and modulates the translation of its RNA ligands. The in vivo targets of the FMRP are beginning to be elucidated and have been shown to include a subset of RNAs with a planar structure called G-quartet.

To study the physiological role of the FMR1 protein, animal models have been developed, including genetically modified mouse and Drosophila. The loss-of-function mouse model shows some features comparable to human patients including enlarged testes, a subtle behavioral phenotype, and discrete anomalies of dendritic spines. Studies in Drosophila indicate that dFmr1 in flies plays an important role in synaptogenesis and axonal arborization, which may underlie the observed deficits in flight ability and circadian rhythm in the dFmr1-mutant flies.

Keywords:

  • Allele;
  • CGG-repeat Expansion;
  • FMR1;
  • FMRP;
  • Fragile Site;
  • Full Mutation;
  • Genotype;
  • Isoforms;
  • Normal Transmitting Male;
  • Phenotypic;
  • Premutation;
  • Ribosome