1/35. Proportion of cells with paternal 11p15 uniparental disomy correlates with organ enlargement in Wiedemann-beckwith syndrome."Genetic mosaicism" describes the presence of two or more populations of cells within a single individual that differ in their genomic constitution. Although the occurrence of asymmetric overgrowth in Wiedemann-Beckwith syndrome (WBS) suggests that mosaicism has some role in the WBS phenotype, no direct evidence for this has been published. WBS is a congenital overgrowth syndrome with variable phenotype linked to the imprinted gene cluster on chromosome region 11p15. We have performed a molecular survey of multiple organs and tissues in a case of WBS with a high degree of mosaic paternal 11p15 uniparental disomy (UPD). The organs most severely affected were those with the highest percentage of cells with UPD. In particular there was a striking difference in the degree of mosaicism for 11p15 UPD between the extremely enlarged left adrenal and non-enlarged right adrenal gland. This result indicates that the proportion of paternal 11p15 UPD cells correlates with the tissue phenotype of WBS. Our results suggest that high proportions of abnormal cells result from a combination of stochastic events and cell selection. mosaicism may explain the variable phenotypes including hemihyperplasia and predisposition to childhood cancers in WBS patients.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
2/35. Subtle familial unbalanced translocation t(8;11)(p23.2;p15.5) in two fetuses with Beckwith-Wiedemann features.We describe a subtle translocation t(8;11)(p23.2;p15.5) ascertained after two induced abortions in the same sibship because of the discovery of fetal hydrops on ultrasound examination. Initial cytogenetic studies performed on cultured amniotic fluid cells were considered as normal in both fetuses. High resolution banding analysis and FISH studies performed on the parents' chromosomes revealed a paternal translocation t(8;11)(p23.2;p15.5). Retrospective FISH analysis of both fetuses showed that they carried the same chromosomal imbalance including a distal monosomy 8pter and a distal trisomy 11pter. The phenotypes of the fetuses were re-examined and found to be compatible with Beckwith-Wiedemann syndromes (BWS). FISH analysis using an IGF2 probe demonstrated the presence of three copies of the IGF2 gene. This study highlights the value of searching for subtle chromosome rearrangements in families with recurrent unexplained multiple malformation syndromes discovered prenatally. Also, it contributes to a better delineation of the prenatal phenotype of BWS. Finally, it sheds new light on the aetiology of non-immune hydrops fetalis.- - - - - - - - - - ranking = 2keywords = chromosome (Clic here for more details about this article) |
3/35. Acrocentric chromosome polymorphisms: beware of cryptic translocations.Cryptic translocations may escape diagnosis, especially when they implicate chromosomal regions that are known to be polymorphic in the human karyotype. We describe a case of postnatal diagnosis of beckwith-wiedemann syndrome (BWS) due to an unbalanced translocation that had not been diagnosed in the fetal karyotype. This first cytogenetic analysis revealed that one chromosome 14 presented as a common acrocentric short arm polymorphism. Further analyses after birth, using C-banding, NOR staining and fluorescence in situ hybridization (FISH) with telomeric probes, revealed that it was the result of an unbalanced de novo t(11;14)(p15;p13) translocation leading to partial 11p trisomy and to BWS. Prenatal cytogenetic management of such apparently inoffensive chromosome markers is discussed.- - - - - - - - - - ranking = 6keywords = chromosome (Clic here for more details about this article) |
4/35. A less-invasive approach with orthodontic treatment in Beckwith-Wiedemann patients.The beckwith-wiedemann syndrome (BWS) is a rare genetic disorder, linked to an alteration on the short arm of chromosome 11 that comprises multiple congenital anomalies. macroglossia is the predominant finding, with subsequent protrusion of dentoalveolar structures, which results in a protruding mandible, anterior open bite, abnormally obtuse gonial angle and increased mandibular length. A less-invasive treatment with orthopaedic appliances in a patient with early tongue reduction is presented. This work summarizes the oral signs linked to macroglossia, and highlights the influence of macroglossia on mandibular growth structures. In our opinion, glossotomy could be carried out in the paediatric patient as a preventive measure in that it curbs the tongue's influence on skeletal growth and dramatically reduces the duration and extensiveness of subsequent treatment.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
5/35. Duplications of chromosome 11p15 of maternal origin result in a phenotype that includes growth retardation.Paternal duplications of distal 11p result in Beckwith Wiedemann syndrome (BWS), whereas maternal duplications have not, to our knowledge, been reported previously in the literature. We present three unrelated patients with maternal duplications of distal 11p. Patient 1 is a 31-year-old female with a de novo inverted duplication of distal 11p, i.e. inv dup del(11)(qter-->p15.5::p15.5-->15.3); this rearrangement was shown to be maternal in origin by microsatellite analysis and methylation-specific polymerase chain reaction. Patient 2 is a 4-year-old female with a derived chromosome 20, which arose from adjacent 1 malsegregation of a maternal t(11;20)(p15.3;q13.33). Patient 3 presented as an intrauterine death with trisomy for the majority of chromosome 11p as a result of 3:1 segregation of a maternal t(11;15)(p11.2;q11.2). In view of the imprinted status of this region, it is pertinent that none of our patients showed features of BWS; indeed, all had growth retardation, in contrast to the overgrowth characteristic of BWS. It is of note that, of the living patients, Patient 1 went into early puberty at 9.5 years and Patient 2 showed breast development in infancy. Both patients shared some dysmorphological features, namely short palpebral fissures, a prominent nasal tip, a short philtrum and 5th finger clinodactyly.- - - - - - - - - - ranking = 6keywords = chromosome (Clic here for more details about this article) |
6/35. Late relapse of adrenocortical carcinoma in beckwith-wiedemann syndrome. Clinical, endocrinological and genetic aspects.We report on a girl with an unusual beckwith-wiedemann syndrome (BWS) and hemihypertrophy, who developed an adrenocortical carcinoma with atypical clinical behaviour. At 4 y of age the girls was admitted to hospital with cushingoid features, virilization, increased excretion of steroids and low serum ACTH. A right-sided adrenocortical carcinoma was removed. At age 12.5 y the cushingoid features reappeared together with a tumour in the left thigh. A CT scan of the thorax and abdomen revealed pulmonary metastasis only. Corticosteroid excretion was increased and serum ACTH level suppressed. The femoral and the pulmonary metastases were removed and histology showed adrenocortical carcinoma. Excretion of corticosteroids subsequently normalized. Meningeal and pulmonary metastases with similar histologies appeared one year later with normal hormone values. Twenty-two months after the recurrence the girl died of an intracranial metastasis. Southern blot analysis of the LITI transcript in the KvLQT1 gene in the BWS region on chromosome 11p15 revealed hypomethylation of the maternal allele. CONCLUSION: adrenocortical carcinoma in childhood may recur years after onset and at rare sites and hormonal levels may be an insufficient indicator of small metastases.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
7/35. Unbalanced translocation of chromosome 3p in Wilms' tumor.Genetic studies in Wilms' tumor have most commonly shown a deletion involving band 13 on the p arm of chromosome 11 in association with aniridia. Structural rearrangements of chromosome 3p have been found in carcinoma of renal cell and lung origin but have not been previously reported in Wilms' tumors. We present two phenotypically normal, unrelated patients with Wilms' tumors, one of which was bilateral, in which cytogenetic analysis of the tumors showed an unbalanced translocation of the p arm of chromosome 3. Two biopsies were done in the patient with bilateral Wilms' tumor. The first biopsy specimen showed a translocation between chromosome 3 and 13 with partial trisomy of 3p and loss of material from 13q. The second biopsy three and a half months later again showed trisomy of chromosome 3p. The unilateral Wilms' tumor showed trisomy of 3p with partial loss of 7p. Neither patient showed a constitutional chromosomal abnormality and neither tumor showed any cytogenetic abnormality involving chromosome 11p. Quantitative dna analysis was performed in the tumors of both patients. The bilateral Wilms' tumor was nearly diploid with a dna index of 1.284 (mean ploidy, 2.45; SD, 0.854) while the unilateral Wilms' tumor was aneuploid with a dna index of 1.531 (mean ploidy, 3.35; SD, 0.976). dna analysis results are discussed in relationship to the chromosome abnormality seen on the karyotype analysis. These cytogenetic findings suggest that genetic oncogenesis in Wilms' tumor is heterogenous.- - - - - - - - - - ranking = 11keywords = chromosome (Clic here for more details about this article) |
8/35. beckwith-wiedemann syndrome-associated hepatoblastoma: wnt signal activation occurs later in tumorigenesis in patients with 11p15.5 uniparental disomy.beckwith-wiedemann syndrome (BWS) patients with chromosome 11p15.5 uniparental isodisomy (UPD) have an increased risk for developing embryonal tumors. UPD in these patients involves maternal loss of heterozygosity (LOH) and paternal duplication, which leads to tissue overgrowth and tumor development. Although 11p15.5 UPD predisposes to tumorigenesis, the events leading to tumorigenesis in UPD patients remains unknown. We have examined two hepatoblastomas in the BWS patients with UPD to determine the sequence of genetic events. Constitutional 11p15.5 LOH was detected in the blood or nonneoplastic liver of the BWS patients with hepatoblastoma. mutation of beta-catenin gene (CTNNB1) was found in one hepatoblastoma. Although mutations in CTNNB1 were not found in the second hepatoblastoma, nuclear accumulation of beta-catenin was detected. However, mutation of CTNNB1 or nuclear accumulation of beta-catenin was not detected in the tissue with hepatomegaly which contains UPD cells. These data indicate that Wnt signal activation can be involved as a later event in BWS-associated hepatoblastoma involving 11p15.5 UPD.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
9/35. beckwith-wiedemann syndrome due to 11p15.5 paternal duplication associated with klinefelter syndrome and a "de novo" pericentric inversion of chromosome Y.We report on an infant who had been prenatally diagnosed with klinefelter syndrome associated with a "de novo" pericentric inversion of the y chromosome. A re-evaluation at 3 years of age suggested that he was also affected by beckwith-wiedemann syndrome (BWS). karyotype was repeated and fluorescence in situ hybridisation (FISH) analysis revealed trisomy for 11p15.5-->11pter and a distal monosomy 18q (18q23-->qter). Parental cytogenetic studies showed that the father carried a balanced cryptic translocation between chromosomes 11p and 18q. Furthermore, the child had an extra x chromosome and a "de novo" structural abnormality of chromosome Y. Thus, his karyotype was 47,XX, inv (Y) (p11.2 q11.23), der(18) t (11;18) (p15.5;q23) pat. ish der(18) (D11S2071 , D18S1390-). Two markers on the x chromosome showed that the extra X of the child was paternally inherited. No deletions were observed on the structurally abnormal y chromosome from any of the microsatellites studied. Clinical findings of patients with BWS due to partial trisomy 11p reveal that there is a distinct pattern of dysmorphic features associated with an increased incidence of mental retardation when comparing patients with normal chromosomes. This fact reinforces that FISH study have to be performed in all BWS patients, specially in those with mental retardation since small rearrangements cannot be detected by conventional cytogenetic techniques.- - - - - - - - - - ranking = 11keywords = chromosome (Clic here for more details about this article) |
10/35. Monozygotic twinning and Wiedemann-Beckwith syndrome.Monozygotic (MZ) twinning occurs with relatively high frequency in Wiedemann-Beckwith syndrome (WBS). Ten sets of MZ twins with WBS have been reported. Nine of these have been female and in each case the twins were discordant for the WBS phenotype. The tenth set was male. They were concordant for WBS and both had a duplication of chromosome 15 which they shared in common with their phenotypically normal mother. The WBS gene has been assigned to the locus 11p15 and there appear to be several different genetic mechanisms involving this locus which all give rise to WBS. An imprinting effect for the WBS gene has been proposed because of the transmission of the gene preferentially through the maternal line in some large pedigrees. We describe two further sets of female MZ twins with WBS. One pair is concordant and one discordant for the condition. The possible genetic mechanisms involved in the expression of WBS are discussed, with particular reference to twinning, genomic imprinting and X-inactivation which is thought to be associated with the occurrence of MZ twinning in females.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
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