Mental retardation, FRA12A type (DIP2B)
| Dred_ID | RD00038 |
| OMIM ID | 136630 |
| Disease name | Mental retardation, FRA12A type |
| Alternative names | FRA12A |
| Category | Genetic diseases, Neuronal diseases, Mental diseases |
| Phenotype | OMIM: FRA12A is a folate-sensitive chromosomal fragile site prone to breakage. No consistent phenotype has been observed with FRA12A, and it can be inherited without phenotypic effect (Berg et al., 2000). However, mental retardation with or without other anomalies has been described in patients with over 40% of cells expressing FRA12A (Winnepenninckx et al., 2007). |
| Miscellaneouse | OMIM: variable phenotype |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | Yes |
| Evidence | Strong |
| Gene symbol | DIP2B |
| Alias symbols | DIP2B |
| Gene name | DIP2 disco-interacting protein 2 homolog B |
| Gene map locus | 12q13.12; chr12:50,504,985-50,748,657(+) |
| Ensembl Gene ID | ENSG00000066084 |
| 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 member of the disco-interacting protein homolog 2 protein family. The encoded protein contains a binding site for the transcriptional regulator DNA methyltransferase 1 associated protein 1 as well as AMP-binding sites. The presence of these sites suggests that the encoded protein may participate in DNA methylation. This gene is located near a folate-sensitive fragile site, and CGG-repeat expansion in the promoter of this gene which affects transcription has been detected in individuals containing this fragile site on chromosome 12. [provided by RefSeq, Aug 2011] |
| Repeat unit | CGG |
| Normal repeat copies | 12-26 |
| Pathogenic repeat copies | ≥151 |
| Gene | DIP2B |
| Repeat location | 5' UTR |
| Chromosome locus | chr12:50505004-50505027 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | In patients with FRA12A, the authors identified an elongated polymorphic CGG repeat in the 5-prime untranslated region of the DIP2B gene (611379.0001), which encodes a protein with a DMAP1 (605077) binding domain, suggesting a role in DNA methylation machinery. DIP2B mRNA levels were halved in 2 subjects with FRA12A with mental retardation in whom the repeat expansion was methylated. In 2 individuals without mental retardation but with an expanded and methylated repeat, DIP2B expression was reduced to approximately two-thirds of the values observed in controls. A carrier of an unmethylated CGG repeat expansion showed increased levels of DIP2B mRNA, which suggested that the repeat elongation increases gene expression, as previously described for the fragile X-associated tremor/ataxia syndrome (300623). The data suggested that deficiency of DIP2B, a brain-expressed gene, may mediate the neurocognitive problems associated with FRA12A. [by OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 17236128 |
| Authors | Winnepenninckx B, Debacker K, Ramsay J, Smeets D, Smits A, FitzPatrick DR, Kooy RF |
| Title | CGG-repeat expansion in the DIP2B gene is associated with the fragile site FRA12A on chromosome 12q13.1 |
| Journal | Am J Hum Genet. 80(2):221-31 |
| Year | 2007 |