Fragile X syndrome

Irissa M. Devine, Carl E. Stafstrom

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Definitions, genetics, and epidemiology Fragile X syndrome is the most frequent cause of familial mental retardation and the second most common overall cause of mental retardation after Down syndrome. The prevalence of fragile X syndrome has not been uniformly defined, but is estimated to be approximately 1 in 4000 in males and 1 in 8000 in females (Crawford et al. 2001). Fragile X syndrome comprises one-fourth to one-third of patients with X-linked mental retardation. Fragile X syndrome is an X-linked dominant disorder with reduced penetrance. It is named for the presence of an unstable chromosomal site on the long arm of chromosome X (Lubs 1969; Sutherland 1977). Typical fragile X syndrome is caused by a loss-of-function mutation of the gene FMR1, which is located at chromosome Xq27.3. The mutation leads to amplification of a CGG (cysteine-guanine-guanine) triplet nucleotide repeat in the 5′ untranslated region (exon 1) of FMR1. The result of this mutation is decreased or absent production of fragile X mental retardation protein (FMRP). There are three categories of CGG repeats: unaffected (6–54 repeats), premutation (55–200 repeats), and full mutation (>200 repeats) (Debacker and Kooy 2007). The CGG repeats that cause fragile X syndrome lead to transcriptional silencing of the FMR1 gene, which codes for FMRP; this is an RNA-binding protein that is expressed in a variety of tissues, but is most abundant in neurons. The presence of more than 200 CGG repeats leads to hypermethylation of the gene, causing reduced gene transcription, and thus a reduction or absence of FMRP synthesis.

Original languageEnglish (US)
Title of host publicationThe Causes of Epilepsy
Subtitle of host publicationCommon and Uncommon Causes in Adults and Children
PublisherCambridge University Press
Pages272-276
Number of pages5
ISBN (Electronic)9780511921001
ISBN (Print)9780521114479
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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