Fragile X Tremor/ataxia Syndrome (FMR1)
| Dred_ID | RD00034 |
| OMIM ID | 300623 |
| Disease name | Fragile X Tremor/ataxia Syndrome |
| Alternative names | Fxtas Syndrome Fxtas Fragile X-Associated Tremor/ataxia Syndrome |
| Category | Genetic diseases, Neuronal diseases, Rare diseases |
| Phenotype | OMIM: Jacquemont et al. (2007) provided a review of fragile X syndrome, which they characterized as a neurodevelopmental disorder, and FXTAS, which they characterized as a neurodegenerative disorder. Amiri et al. (2008) provided a review of FXTAS and noted that the pathogenesis of the disorder is distinct from that in fragile X syndrome. FXTAS results form a toxic gain of function of FMR1 RNA, whereas fragile X syndrome results from a loss of FMR1 function. The penetrance of FXTAS in male carriers aged 50 years and over, ascertained through families with a fragile X syndrome proband, is at least 33% (Hagerman and Hagerman, 2004); its penetrance in female carriers is approximately 5-10% (Greco et al., 2008). (300623) |
| Miscellaneouse | OMIM: onset in fifties or sixties caused by 55-200 expanded trinucleotide repeats in the fmr1 gene referred to as a 'premutation' most patients have a family history of fragile x syndrome full mutations with expanded trinucleotide repeats greater than 200 result in fragile x mental retardation syndrome males are more commonly affected than females |
| Prevalence | 1-9/100000 (United States) [source: MalaCards] |
| Inheritance | X-linked dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | FMR1 |
| Alias symbols | POF; FMRP; POF1; FRAXA |
| Gene name | fragile X mental retardation 1 |
| Gene map locus | Xq27.3; 147,911,919-147,951,125(+) |
| Ensembl Gene ID | ENSG00000102081 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010] |
| Repeat unit | CGG |
| Normal repeat copies | <55 |
| Pathogenic repeat copies | 55-200 |
| Gene | FMR1 |
| Repeat location | 5' UTR |
| Chromosome locus | chrX:147912051-147912113 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Arocena et al. (2005) noted that FXTAS appears to affect only carriers of premutation alleles, who have normal or near-normal FMR1 protein levels in both peripheral blood leukocytes and brain tissue, suggesting that FXTAS may result from a toxic gain-of-function of the FMR1 mRNA itself. In human neural SK cells, expression of an 88-repeat premutation allele resulted in development of inclusions containing the heat shock protein alpha-B-crystallin (CRYAB; 123590) and lamin A/C (LMNA; 150330). The expanded FMR1 repeat was cytotoxic. The findings suggested that the neuropathology of FXTAS may be mediated in part by dysregulation of lamin A/C function, which would be consistent with the peripheral neuropathy that is common among FXTAS patients. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 22017584 |
| Authors | Santoro MR, Bray SM, Warren ST. |
| Title | Molecular Mechanisms of Fragile X Syndrome: A Twenty-Year Perspective |
| Journal | Annu Rev Pathol. 7:7:219-245 |
| Year | 2012 |
| PMID | 15052536 |
| Authors | Hagerman PJ, Hagerman RJ. |
| Title | The fragile-X premutation: a maturing perspective |
| Journal | Am J Hum Genet. 75(2):352 |
| Year | 2004 |