JBS_CBL
- Gene
- CBL
- Disease
- JBS
- Inheritance
- AD
- Classification
- Definitive
- Total Score
- 14.5
- Publications Reviewed
- 3
- Publication Span
- 5.17 years
- Last Updated
- 08/12/2025
- Curator(s)
- Macayla, Laurel
Description
Jacobsen syndrome (JBS) is a contiguous-gene disorder caused by partial deletion of the distal long arm of chromosome 11. The FRA11B CCG repeat/fragile site at 11q23.3, located at the 5' end/immediately upstream of CBL/CBL2, has been implicated as a breakage-prone locus in a subset of JBS cases. The uploaded evidence supports a mechanism in which CCG repeat expansion and associated fragile-site instability can lead to downstream 11q deletion, rather than a CBL coding-variant mechanism.
Genetic evidence
Total: 12
| Singular Evidence | Probands | PMID:7603564 | 6 | PMID:7603564 reported two Jacobsen syndrome cases/families in which the deleted 11q chromosome derived from a chromosome carrying an expanded CBL2 p(CCG)n/FRA11B allele; the chromosome truncation occurred close to FRA11B. |
| Singular Evidence | Probands | PMID:7887422 PMID:10767345 | 6 | PMID:7887422 studied 17 individuals with de novo terminal 11q deletions; eight patients with the largest 11q23.3-to-11qter deletions had breakpoints between D11S924 and D11S1341, a region related to FRA11B. PMID:10767345 collated deletion mapping from 24 Jacobsen patients and additional cases, showing non-random co-localization of mapped deletion breakpoints with CCG-repeat-containing YAC/PAC clones in distal 11q. |
2 rows
Experimental evidence
Total: 2.5
| Function | Biochemical function | PMID:7603564 | 0.5 | PMID:7603564 localized FRA11B to the CBL2 p(CCG)n repeat by FISH and Southern/PCR analyses, supporting a locus-specific fragile-site/chromosome-breakage mechanism rather than CBL protein biochemical function. |
| Function | Regulatory impact | PMID:7603564 PMID:10767345 | 1 | PMID:7603564 showed expansion of the CBL2 p(CCG)n repeat in FRA11B-expressing chromosomes and methylation of the adjacent CBL2 CpG island when repeat length exceeded fragile-site thresholds. PMID:10767345 supports CCG-repeat expansion/hypermethylation and replication-delay/secondary-structure mechanisms as contributors to chromosome breakage. |
| Functional Alteration | Patient cells | PMID:7603564 PMID:10767345 | 1 | PMID:7603564 used patient/family-derived blood lymphocytes and an EBV-transformed cell line from a FRA11B-expressing individual to demonstrate CBL2 p(CCG)n expansion, adjacent CpG methylation, and 11q deletion breakpoint localization near FRA11B; PMID:10767345 further mapped JBS breakpoints in patient-derived material to CCG-repeat-containing clones. |
3 rows
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.