Disease relevance of FRA11B

• The result also distinguishes the FRA11B locus from the site of translocation at 11q23-q24 in the Ewing sarcoma- and peripheral neuroepithelioma-specific t(11;22), indicating that the chromosomes of a previously reported patient heterozygous for fra(11)(q23) did not rearrange at this fragile site to give rise to Ewing sarcoma [1].

High impact information on FRA11B

• A proportion of Jacobsen (11q-) syndrome patients inherited a chromosome carrying a CBL2 p(CCG)n expansion, which was truncated close to FRA11B [2].
• This cytogenetic region accounts for the majority of 11q- patients and may be related to the FRA11B fragile site in 11q23 [3].
• Physical linkage of the fragile site FRA11B and a Jacobsen syndrome chromosome deletion breakpoint in 11q23.3 [4].
• However, one case report has highlighted a possible relationship between the inheritance of a rare folate-sensitive fragile site in band 11q23.3 (FRA11B) and the chromosome 11q23-->qter deletion in Jacobsen (11q-) syndrome [4].
• We have tested this hypothesis by high resolution physical mapping of FRA11B and of the deletion chromosome breakpoint in the Jacobsen syndrome patient [4].

Biological context of FRA11B

• The fragile site FRA11B has been localized to the p(CCG)n repeat of the CBL2 proto-oncogene [2].
• FISH experiments with YACs and cosmids from this region have localised FRA11B to an interval of approximately 100 kb containing the 5' end of the CBL2 gene, which includes a CCG trinucleotide repeat [4].
• A genetic etiology is indicated by an association of the hypoplastic left heart phenotype with terminal 11q deletions that span approximately 20 Mb (distal to FRA11B in 11q23) [5].
• In both cases, microsatellite and fluorescence in situ hybridization analyses indicated that the deletion breakpoint was approximately 1.5-3 Mb telomeric to FRA11B [6].
• In conclusion, leukaemogenesis in infants is a rare event, arising in stem cells of very early hematopoietic differentiation (probably due to gene rearrangement errors, most frequently at FRA11B), and differs from leukaemogenesis in older age groups by unique clinical and cellular features [7].

Associations of FRA11B with chemical compounds

• Fluorescence in situ hybridization studies on the first patient placed the two breakpoints near the folate-sensitive fragile sites FRA11A and FRA11B [8].

Other interactions of FRA11B

• 3. This result localizes ETS1 from the FRA11B locus to 11q24 [1].
• In dealing with patients who are found to have fragile sites, other than FRAXA, FRAXE and possibly FRA11B, considerable reassurance can be given that they are not at increased risk of having children with congenital disease or developing disease themselves because of their fragile sites [9].
• It is doubtful that parents with FRA11B are at increased risk of having children with Jacobsen syndrome, but this cannot be ruled out [9].
• These were high length (but not expanded) repeats at FRA11B (P = 0.01), ATXN1 (P = 0.032) and ATXN3 (P = 0.022), all associated with poor risk disease [10].
• The chromosomal subband 11q23.3 harbors both the common fragile site FRA11G and the rare fragile site FRA11B [11].

References