Curation JBS CBL

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.

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.

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.

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.

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.