|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
We describe a family with overgrowth in three generations and Wilms' tumor in two generations, with paternal inheritance of a cis-duplication at 11p15.5 spanning the BWS IC1 region and including H19, IGFII, INS, and TH.
|
17325026 |
2007 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
In order to screen for other genetic predispositions to BWS, the conserved sequences between human and mouse differentially methylated regions (DMRs) of the IGF2 gene were analyzed for variants.
|
14645199 |
2004 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The same region includes IGF2 and CDKN1C and is well known to harbour alterations in patients suffering from Beckwith-Wiedemann syndrome.
|
15234339 |
2004 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Maternal transmission of the deletions results in hypermethylation of the H19 DMR, biallelic IGF2 expression, H19 silencing and Beckwith-Wiedemann syndrome, indicative of loss of function of the IGF2-H19 imprinting control element.
|
15314640 |
2004 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
For example, loss of proper imprinting control at the IGF2-H19 domain is a hallmark of cancer and Beckwith-Wiedemann syndrome, with no targeted therapeutic approaches available.
|
12621455 |
2003 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
The subtelomeric region of 11p harbours three closely linked genes, TH, INS and IGF2, that have been associated with obesity, size at birth, type I diabetes, polycystic ovary syndrome, overgrowth in Beckwith-Wiedemann syndrome and possibly hypertension.
|
11935324 |
2002 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
Many imprinted genes contribute to growth, either as growth factors, such as insulin-like growth factors (IGF2 in Beckwith-Wiedemann syndrome), or as growth inhibitors, such as the GRB10 gene in Russell-Silver syndrome.
|
12510981 |
2002 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
PosttranslationalModification
|
disease |
BEFREE |
Nesidioblastosis and mixed hamartoma of the liver in Beckwith-Wiedemann syndrome: case study including analysis of H19 methylation and insulin-like growth factor 2 genotyping and imprinting.
|
11441340 |
2001 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
Loss of imprinting (LOI) of insulin-like growth factor-2 (IGF-2) has been implicated in the pathogenesis of certain human cancers and tumor-predisposing overgrowth disorders, such as Beckwith-Wiedemann syndrome.
|
10820361 |
2000 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
These results indicate that in BWS, (1) H19 imprinting alterations are less frequent than previously estimated, (2) IGF2 imprinting and H19 imprinting are not necessarily coordinated, and (3) alterations in regional replication timing are generally not correlated with either chromosomal rearrangements or the imprinting status of IGF2 and H19.
|
10857747 |
2000 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Recently, we showed that a subgroup of BWS patients have loss of methylation (LOM) at a differentially methylated region (KvDMR1) within the KCNQ1 gene centromeric to the IGF2 and H19 genes.
|
11106355 |
2000 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
These data suggest that the effects of increased IGF-II in BWS may, in part, be mediated through a decrease in p57(kip2) gene expression.
|
10779549 |
2000 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
To understand how the same disease can result from misregulation of two linked, but unrelated, genes, we generated a mouse model for BWS that both harbors a null mutation in p57(Kip2) and displays loss of Igf2 imprinting.
|
10601037 |
1999 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Such increased IGF-II expression would appear to explain the overgrowth in Beckwith-Wiedemann syndrome.
|
10102049 |
1999 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II.
|
10402475 |
1999 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
Surprisingly, LOI of LIT1 was not linked to LOI of insulin-like growth factor II (IGF2), which was found in 2 of 10 (20%) BWS patients, even though LOI of IGF2 occurs frequently in Wilms and other tumors, and in some patients with BWS.
|
10220444 |
1999 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
BWS is genetically heterogeneous and epigenetic changes in the IGF2/H19 genes resulting in overexpression of IGF2 have been implicated in many cases.
|
10424811 |
1999 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Loss of imprinting at IGF2, generally through an H19-independent mechanism, is associated with a large percentage of patients with the overgrowth and cancer predisposition condition Beckwith-Wiedemann syndrome (BWS).
|
10393948 |
1999 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
Relaxation of IGF2 imprinting occurs in the Beckwith-Wiedemann syndrome of somatic overgrowth, sporadic Wilms' tumour and a number of other cancers.
|
9722981 |
1998 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
The association of a chromosome 18 deletion and BWS may be coincidental or may indicate the location of a trans activating regulator element for maintenance of IGF2 imprinting.
|
9507400 |
1998 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
A phenotypically related X-linked overgrowth syndrome, Simpson Golabi Behmel syndrome (SGBS), is caused by alterations in glypican-3 (GPC3), a molecule that may interact with the gene products identified to be important in generating the BWS phenotype, that is, IGF2 and p57KIP2.
|
9630066 |
1998 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
PosttranslationalModification
|
disease |
BEFREE |
We previously mapped BWS, by genetic linkage analysis, to 11p15.5, which we and others also found to contain several imprinted genes; these include the gene for insulin-like growth factor II (IGF2) and H19, which show abnormal imprint-specific expression and/or methylation in 20% of BWS patients, and p57KIP2, a cyclin-dependent kinase inhibitor, which we found showed biallelic expression in one of nine BWS patients studied.
|
9311734 |
1997 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
These phenotypes establish Igf2 overexpression as a key determinant of Beckwith-Wiedemann syndrome.
|
9349812 |
1997 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
Biomarker
|
disease |
BEFREE |
Analysis of H19 methylation is useful for the diagnosis of both UPD or altered imprinting in BWS and shows that a variety of molecular mechanisms may cause relaxation of IGF2 imprinting in BWS.
|
9152830 |
1997 |
|
Beckwith-Wiedemann Syndrome
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We have examined the allele-specific expression of IGF2 and H19 in fibroblasts derived from patients with sporadic Beckwith-Wiedemann syndrome (BWS), a fetal overgrowth syndrome associated with an imprinted locus on 11p15.5.
|
9285792 |
1997 |