11/35. New chromosome 11p15 epigenotypes identified in male monozygotic twins with beckwith-wiedemann syndrome.beckwith-wiedemann syndrome (BWS) is an overgrowth syndrome demonstrating heterogeneous molecular alterations of two imprinted domains on chromosome 11p15. The most common molecular alterations include loss of methylation at the proximal imprinting center, IC2, paternal uniparental disomy (UPD) of chromosome 11p15 and hypermethylation at the distal imprinting center, IC1. An increased incidence of female monozygotic twins discordant for BWS has been reported. The molecular basis for eleven such female twin pairs has been demonstrated to be a loss of methylation at IC2, whereas only one male monozygotic twin pair has been reported with this molecular defect. We report here two new pairs of male monozygotic twins. One pair is discordant for BWS; the affected twin exhibits paternal UPD for chromosome 11p15 whereas the unaffected twin does not. The second male twin pair is concordant for BWS and both twins of the pair demonstrate hypermethylation at IC1. Thus, this report expands the known molecular etiologies for BWS twins. Interestingly, these findings demonstrate a new epigenotype-phenotype correlation in BWS twins. That is, while female monozygotic twins with BWS are likely to show loss of imprinting at IC2, male monozygotic twins with BWS reflect the molecular heterogeneity seen in BWS singletons. These data underscore the need for molecular testing in BWS twins, especially in view of the known differences among 11p15 epigenotypes with respect to tumor risk.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
12/35. Microarray detection of a de novo der(X)t(X;11)(q28;p13) in a girl with premature ovarian failure and features of beckwith-wiedemann syndrome.We report an 18-year-old girl with premature ovarian failure (POF), tall stature, and urinary incontinence. Chromosome studies including array comparative genomic hybridization showed that she was the carrier of an unbalanced de novo translocation between the x chromosome and chromosome 11, resulting in partial monosomy Xq and partial trisomy 11p. Microsatellite analysis demonstrated that the patient had paternal duplication of 11p13p15.5, which contributed to some of her features consistent with beckwith-wiedemann syndrome (BWS). The combined phenotype of BWS and POF suggests that the translocated portion of 11p remains active.- - - - - - - - - - ranking = 0.28571428571429keywords = chromosome (Clic here for more details about this article) |
13/35. The centromeric 11p15 imprinting centre is also involved in silver-russell syndrome.silver-russell syndrome (SRS) is a heterogeneous disorder characterised by severe intrauterine and postnatal growth retardation, limb and body asymmetry, a typical facial appearance and less common dysmorphisms. Recently, epimutations and maternal duplications affecting the short arm of chromosome 11 have been shown to have a crucial role in the aetiology of the disease. Disturbances in the same genomic region cause the overgrowth disorder beckwith-wiedemann syndrome (BWS). In BWS, mutations in the telomeric as well as in the centromeric imprinting centres (ICR1 and ICR2) in 11p15 can be observed. In SRS, methylation defects in the imprinted region in 11p15 were considered to be restricted to the telomeric ICR1. They can be detected in about 30% of patients. This article reports on the first patient with SRS with a cryptic duplication restricted to the centromeric ICR2 domain in 11p15. The maternally inherited duplication in this patient included a region of 0.76-1 Mbp and affected the genes regulated by the ICR2, among them CDKN1C and LIT1. This study provides evidence for a role for this imprinting centre in the aetiology of SRS and shows that SRS presents a picture genetically opposite to that of BWS.- - - - - - - - - - ranking = 0.14285714285714keywords = chromosome (Clic here for more details about this article) |
14/35. beckwith-wiedemann syndrome presenting with an elevated triple screen in the second trimester of pregnancy.BACKGROUND: beckwith-wiedemann syndrome (BWS) is a distinct clinical syndrome with unique features, generally diagnosed postnatally. CASE: A 26-year-old patient, gravida 4, para 3-0-0-3, was noted to have an abnormal maternal serum screen. amniocentesis with imaging studies were remarkable only for a two-vessel umbilical cord and prominent maternal ovaries. The patient developed hellp syndrome at 28 weeks and delivered a viable female infant with distinct clinical features. The diagnosis of BWS was confirmed by hypermethylation of the H19 gene on chromosome 11p15.5. CONCLUSION: This case describes a novel presentation of BWS and underscores the diagnostic potential of routine prenatal screens.- - - - - - - - - - ranking = 0.14285714285714keywords = chromosome (Clic here for more details about this article) |
15/35. Jacobsen syndrome and beckwith-wiedemann syndrome caused by a parental pericentric inversion inv(11)(p15q24).Here we report on a male infant presenting the typical pattern of Jacobsen syndrome including trigonocephaly, thrombocytopenia, congenital heart defect, urethral stenosis, and partial agenesis of the corpus callosum. Conventional karyotyping, FISH, SKY and CGH analyses showed that the region distal to the MLL locus on 11q23 was lost and replaced by the distal region of 11p, leading to a partial trisomy of 11p and a partial monosomy of 11q. According to ISCN (1995) the karyotype can be described as 46,XY,add(11)(q2?3). ish 11ptel(D11S2071x3),11qtel(VIJyRM2072x1). Array-CGH analysis allowed us to narrow down the breakpoints to 11p15.1 and 11q24.1. methylation analyses of genes located on 11p showed an increased level of the non-methylated paternal allele of the KCNQ1OT1 gene, confirming the concomitant presence of beckwith-wiedemann syndrome (BWS). The phenotype resulting from the 11q deletion seems to dominate the phenotype due to the distal 11p trisomy. Investigation of the parents revealed that this chromosomal rearrangement was caused by a paternal pericentric inversion inv(11)(p15q24). Since chromosomal aberrations like the one described here can easily be overlooked during routine chromosome analysis, combined FISH analysis using subtelomeric and possibly additional probes should be applied if there is any doubt about the integrity of telomeric regions.- - - - - - - - - - ranking = 0.14285714285714keywords = chromosome (Clic here for more details about this article) |
16/35. Paternal origin of 11p15 duplications in the beckwith-wiedemann syndrome. A new case and review of the literature.A boy suffering from the beckwith-wiedemann syndrome (BWS) was found to have partial trisomy of the short arm of chromosome 11 [46,XY,der(5)t(5;11)(p15.2;p14)]. Both his parents were phenotypically normal, but his father carried a balanced translocation between chromosomes 5 and 11 [46,XY,t(5;11)(p15.2;p14)]. dna analysis of polymorphic markers on 11p15 confirmed the paternal origin of the duplicated material in the child. This case is the sixth report of paternal duplication of 11p15 in BWS. These results are discussed in relation to the possible role of genomic imprinting in BWS and in Wilms' tumor.- - - - - - - - - - ranking = 0.28571428571429keywords = chromosome (Clic here for more details about this article) |
17/35. Balanced reciprocal translocation (X;20) limited to Wilms' tumor in a Wiedemann-Beckwith syndrome.A girl aged 4 years 3 months with sporadic unilateral Wilms' tumor associated with Wiedemann-Beckwith syndrome, but without aniridia, was found to have a t(X;20) in the tumor cells. Karyotypes of peripheral blood of the patient and her parents were normal. This translocation was confined to the tumor and not been previously reported either in nephroblastoma or any other neoplastic processes. Although there is no microscopic deletion on chromosome 11 and catalase activity was not decreased, we cannot rule out the possibility of a point mutation or a submicroscopic deletion.- - - - - - - - - - ranking = 0.14285714285714keywords = chromosome (Clic here for more details about this article) |
18/35. genetic linkage of beckwith-wiedemann syndrome to 11p15.beckwith-wiedemann syndrome (BWS), characterized by multiorgan developmental abnormalities and predisposition to cancer, usually occurs sporadically, but small apparently dominant pedigrees have been described. Since rare patients show varying karyotypic abnormalities on the short arm of chromosome 11, it has been suggested that BWS may be related to the wilms tumor gene on 11p13 or, alternatively, to growth factor genes on 11p15. We performed genetic linkage analysis on two BWS kindreds, using RFLPs for loci on 11p. BWS was linked to the insulin gene (11p15.5), with an overall maximum lod score of 3.60 (recombination fraction = .00). Linkage to D11S16 (11p13) could be excluded for recombination fractions less than or equal to .03. These results suggest that BWS defines a tumor-predisposition gene on 11p15.- - - - - - - - - - ranking = 0.14285714285714keywords = chromosome (Clic here for more details about this article) |
19/35. Analysis of gene dosage on chromosome 11 in children suffering from beckwith-wiedemann syndrome.The beckwith-wiedemann syndrome (BWS) is composed of multiple congenital malformations coupled with a high concurrent risk for the development of specific rare childhood tumours. The syndrome is characterised by a complex mode of inheritance, but recent evidence indicates that it is an autosomal dominant trait with variable penetrance. It has been previously suggested that major rearrangements of the short arm of chromosome 11 are involved in the aetiology of the disease. We undertook to search for rearrangements in 11p in four patients with BWS and their parents and siblings. By using cloned dna fragments homologous to four genes located on 11p, namely catalase, parathyroid hormone, insulin-like growth factor II and the proto-oncogene c-Ha-Ras, we subjected dna from the patients to a restriction fragment length polymorphism (RFLP) analysis after digestion with restriction enzymes. We found no evidence for any large scale deletions or amplifications in this chromosomal region. We therefore conclude that altered gene dosage is not, as has been suggested, a requirement for the development of BWS. This raises the question of whether some other molecular mechanism is responsible for the malformations observed.- - - - - - - - - - ranking = 0.71428571428571keywords = chromosome (Clic here for more details about this article) |
20/35. Loss of alleles on the short arm of chromosome 11 in a hepatoblastoma from a child with beckwith-wiedemann syndrome.The beckwith-wiedemann syndrome (BWS) is characterised by multiple congenital abnormalities, including exomphalos, macroglossia, and gigantism. It is also associated with an elevated risk of embryonal neoplasia and occasionally with constitutional anomalies of chromosome band 11p15. A common pathogenetic mechanism for the development of several embryonal tumours has been proposed involving the loss of somatic heterozygosity for a locus on the short arm of chromosome 11. In support of this hypothesis, we have recently reported generation of homozygosity for the c-Ha-ras-1 protooncogene in an adrenal adenoma from an adult BWS patient. In this study we report the generation of homozygosity for a region on the short arm of chromosome 11 defined by the calcitonin (11p13-15) and insulin (11p15-15.1) genes in a hepatoblastoma from a child with BWS.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
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