Fragile Sites at 16q22 Are Not at the Breakpoint of the Chromosomal Rearrangement in AMMoL

Simmers, R N; Sutherland, G. R.; West, Adrian K.; Richards, R.I.

doi:10.1126/science.3470945

Cited by 55 publications

(20 citation statements)

References 27 publications

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“…1f, g) which supported the view that FRA16B is a chromosome site with properties of high somatic recombination (Schmid et al, 1987). However, it has been demonstrated that a specific leukemic breakpoint is, in fact, located proximal to FRA16B (Simmers et al, 1987). Most importantly, individuals heterozygous and homozygous for FRA16B are generally normal (Fig.…”

Section: Clinical Impact Of Fra16bmentioning

confidence: 99%

The rare human fragile site 16B

Felbor¹,

Feichtinger²,

Schmid³

2003

Cytogenet Genome Res

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The rare human fragile site 16B (FRA16B) has been found to occur spontaneously. Its expression in lymphocyte cultures can also be induced or greatly enhanced by addition of chemicals which are known to bind to AT-rich DNA regions. Following optimal treatment with 150 µg/ml berenil 24 h prior to fixation, the heterozygote frequency of FRA16B is found to be about 5% in populations of European descent. Thus, FRA16B represents the most common of the rare fragile sites. Consistent with cytogenetic observations, the molecular characterization of FRA16B revealed that it is an amplified 33-base pair AT-rich minisatellite repeat. These interindividually variable, extremely large repeat expansions of 15–70 kb in size do not seem to interfere with the expression of genes essential for human development since heterozygotes and homozygotes for FRA16B are normal.

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Section: Clinical Impact Of Fra16bmentioning

confidence: 99%

The rare human fragile site 16B

Felbor¹,

Feichtinger²,

Schmid³

2003

Cytogenet Genome Res

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“…Others have reported the association with MDS [24]. However, defining the exact breakpoints is difficult, and studies with radioactive in situ hybridization show that the breakpoints are not identical, suggesting a coincidental rather than a pathogenetic relationship [25,26]. As indicated by Le Beau, this does not exclude a pathogenetic relationship because the effect of the fragile site on adjacent chromatin is not known [27].…”

Section: Anticipationmentioning

confidence: 99%

Benign chronic neutropenia with abnormalities involving 16q22, affecting mother and daughter

et al. 2006

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We report a case of familial, chronic, benign neutropenia in a 17-year-old female showing (1) the spontaneous expression of a heritable rare fragile site at 16q22 and (2) a deletion at the same region. The del(16)(q22), which most likely originated from the fragile site, was the main clonal abnormality detected in the patient's bone marrow cells, whereas a few cells with either del(16)(q22) or fra(16)(q22) were seen in the patient's peripheral blood. Interestingly, the del(16q) was also detected in the patient's uncultured cells, as demonstrated by FISH, excluding an in vitro origin of the del(16q) during culture. The bone marrow was hypocellular with decreased neutrophils and their precursors. Absolute neutrophil counts ranged from (0.62 to 1.24) 3 10 9 /L with a median value of 1.02 3 10 9 /L. The patient had a more severe neutropenia than her mother, which correlated with the presence of more cells with del(16q) in the marrow. The patient's mother, who was also diagnosed with neutropenia, revealed only a few cells with the rare fra(16)(q22) in her peripheral blood cells, whereas her bone marrow showed cells with both fra(16)(q22) and del(16)(q22), although the del(16q) was present in only 2/20 cells. Some possible candidate genes contributing to the pathogenesis of the neutropenia are discussed. Chromosome abnormalities involving the 16q22 breakpoint have been observed in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this patient, the del(16)(q22) risk factor is unknown for subsequent development of MDS or AML. Another point to consider is the need to determine the origin of a chromosome abnormality, particularly when the clinical picture does not fit the chromosome findings. Although, the observation of a constitutional structural abnormality in a mosaic form is an extremely rare event, it is somewhat different in the case of a fragile site expression, which can, as in this case, be present in some cells and not in others. Am. J. Hematol. 81:262-270, 2006. V V C 2006 Wiley-Liss, Inc.

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“…HEXA, the gene encoding the alpha polypeptide of hexosaminidase A, has been cloned (Myerowitz et al 1985 The evidence for linkage between specific reading disability (SRD1) and the chrom osom e 15 C banding heteromorphism (Smith et al 1983 ;Fain et al 1985) has been reduced further by a recent Danish study (Bisgaard et al 1987). Lod scores were negative throughout with the same marker in 5 families selected from 810 families with dyslexia.…”

Section: Regional Assignmentsmentioning

confidence: 99%

“…The metallothionein gene cluster which comprises at least 14 genes and pseudogenes that can be separated into two groups, MT1 and MT2, and is split by chromosome 16 rearrangements in acute myelomonocytic leukemia (Le Beau et al 1985) has been mapped proximal to FRA16B and FR A 16C by in situ h y b rid iz a tio n w ith two metallothionein-specific probes (Simmers, Sutherland et al 1987). Since Sutherland and coworkers place the fragile sites at the interphase of 16q21 and q22, this may assign MT1 and MT2 to (distal) q21.…”

Section: Regional Assignments and Linkage Datamentioning

confidence: 99%