Jacobsen Syndrome (CBL)
| Dred_ID | RD00033 |
| OMIM ID | 147791 |
| Disease name | Jacobsen Syndrome |
| Alternative names | FRA11B Chromosome 11q Deletion Syndrome Partial 11q Monosomy Syndrome |
| Category | Rare diseases, Eye diseases, Fetal diseases, Blood diseases |
| Phenotype | NIH Rare Diseases: Chromosome 11q deletion is a chromosome abnormality that occurs when there is a missing (deleted) copy of genetic material on the long arm (q) of chromosome 11. The severity of the condition and the signs and symptoms depend on the size and location of the deletion and which genes are involved. Features that often occur in people with chromosome 11q deletion include developmental delay, intellectual disability, behavioral problems and distinctive facial features. Chromosome testing of both parents can provide more information on whether or not the deletion was inherited. In most cases, parents do not have any chromosomal anomaly. However, sometimes one parent is found to have a balanced translocation, where a piece of a chromosome has broken off and attached to another one with no gain or loss of genetic material. The balanced translocation normally does not cause any signs or symptoms, but it increases the risk for having an affected child with a chromosomal anomaly like a deletion. Treatment is based on the signs and symptoms present in each person. This page is meant to provide general information about 11q deletions. You can contact GARD if you have questions about a specific deletion on chromosome 11. To learn more about chromosomal anomalies please visit our GARD webpage on FAQs about Chromosome Disorders. |
| Miscellaneouse | OMIM: contiguous gene deletion syndrome 75% of affected individuals are female incidence of 1 in 100,000 births |
| Prevalence | the birth prevalence has been suggested at 1/50,000-100,000 in the United States [source: MalaCards] |
| Inheritance | Isolated cases |
| Anticipation | N/A |
| Evidence | Weak |
| Gene symbol | CBL |
| Alias symbols | CBL; NSLL; C-CBL; RNF55; FRA11B |
| Gene name | Cbl proto-oncogene |
| Gene map locus | 11q23.3; chr11:119,206,298-119,313,926(+) |
| Ensembl Gene ID | ENSG00000110395 |
| 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 is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016] |
| Repeat unit | CCG |
| Normal repeat copies | 11 |
| Pathogenic repeat copies | ≥101 |
| Gene | CBL |
| Repeat location | 5' UTR |
| Chromosome locus | chr11:119206556-119206564 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | RNA |
| Possible toxicity | Jones et al. (1994) presented evidence consistent with the role of the inherited folate-sensitive fragile site in band 11q23.3, FRA11B (600651), in the etiology of this chromosome deletion syndrome. With fluorescence in situ hybridization experiments using YACs and cosmids from a 600-kb region of 11q23.3, Jones et al. (1994) localized FRA11B to an interval of approximately 100 kb containing the 5-prime end of the CBL2 oncogene (165360), which includes a CCG trinucleotide repeat. Jones et al. (1994) showed that the deletion breakpoint of the Jacobsen syndrome child reported by Voullaire et al. (1987) mapped within the same interval as the fragile site. The breakpoint had apparently been repaired and stabilized by the de novo addition of a telomere. As stated by Jones et al. (1995), who presented further evidence for the role of FRA11B in the generation of the deletion, this was the first demonstration of a direct link between a fragile site and chromosome breakage in vivo. The demonstration of an inherited component in the development of at least some cases of Jacobsen syndrome challenges the dogma that chromosomal deletions and rearrangements associated with clinical manifestations occur de novo, with little or no impact of genetic background. [By OMIM] |
| Pathway annotation | Reactome, KEGG |
| PMID | 10767345 |
| Authors | Jones C, Müllenbach R, Grossfeld P, Auer R, Favier R, Chien K, James M, Tunnacliffe A, Cotter F |
| Title | Co-localisation of CCG repeats and chromosome deletion breakpoints in Jacobsen syndrome: evidence for a common mechanism of chromosome breakage |
| Journal | Hum Mol Genet. 9(8):1201-8 |
| Year | 2000 |
| PMID | 9508241 |
| Authors | Michaelis RC, Velagaleti GV, Jones C, Pivnick EK, Phelan MC, Boyd E, Tarleton J, Wilroy RS, Tunnacliffe A, Tharapel AT. |
| Title | Most Jacobsen syndrome deletion breakpoints occur distal to FRA11B |
| Journal | American Journal of Medical Genetics 76:222–228 |
| Year | 1998 |