Mental Retardation, X-Linked, Associated with Fragile Site Fraxe (AFF2)
| Dred_ID | RD00032 |
| OMIM ID | 309548 |
| Disease name | Mental Retardation, X-Linked, Associated with Fragile Site Fraxe |
| Alternative names | Fraxe Mental Retardation Syndrome Mrfraxe Fraxe Intellectual Disability Fraxe Mental Retardation Syndrome |
| Category | Genetic diseases, Neuronal diseases, Rare diseases, Mental diseases |
| Phenotype | OMIM: FRAXE mental retardation is a form of mild to moderate mental retardation associated with learning difficulties, communication deficits, attention problems, hyperactivity, and autistic behavior (summary by Bensaid et al., 2009). FRAXE is associated with a fragile site on chromosome Xq28 and is the cause of nonsyndromic X-linked mental retardation in 1 of 50,000 newborn males. The disorder can be caused either by silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene or by deletion within the gene (Stettner et al., 2011). (309548) |
| Miscellaneouse | OMIM: occurs in 1 in 50,000 newborn males |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | X-linked recessive |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | AFF2 |
| Alias symbols | FMR2; MRX2; OX19; FMR2P; FRAXE |
| Gene name | AF4/FMR2 family member 2 |
| Gene map locus | Xq28; chrX:148,500,617-149,000,663(+) |
| Ensembl Gene ID | ENSG00000155966 |
| 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 | This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016] |
| Repeat unit | CCG |
| Normal repeat copies | 4-39 |
| Pathogenic repeat copies | ≥201 |
| Gene | AFF2 |
| Repeat location | 5' UTR |
| Chromosome locus | chrX:148500639-148500686 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | The FMR1 mRNA contains the transcribed CGG-repeat tract as part of the 5' untranslated region, which hybridizes to the complementary CGG-repeat portion of the FMR1 gene to form an RNA·DNA duplex. Disrupting the interaction of the mRNA with the CGG-repeat portion of the FMR1 gene prevents promoter silencing. Thus, our data link trinucleotide-repeat expansion to a form of RNA-directed gene silencing mediated by direct interactions of the trinucleotide-repeat RNA and DNA. [By PMID: 24578575] |
| Pathway annotation | Reactome, KEGG |
| PMID | 21330300 |
| Authors | Melko M, Douguet D, Bensaid M, Zongaro S, Verheggen C, Gecz J, Bardoni B. |
| Title | Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability |
| Journal | Hum Mol Genet. 20(10):1873-85 |
| Year | 2011 |
| PMID | 19136466 |
| Authors | Bensaid M, Melko M, Bechara EG, Davidovic L, Berretta A, Catania MV, Gecz J, Lalli E, Bardoni B. |
| Title | FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure |
| Journal | Nucleic Acids Res. 37(4):1269-79 |
| Year | 2009 |