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Wiedemann Syndrome (wiedemann + syndrome)
Selected AbstractsRapid detection of methylation change at H19 in human imprinting disorders using methylation-sensitive high-resolution melting,HUMAN MUTATION, Issue 10 2008Tomasz K. Wojdacz Abstract Beckwith Wiedemann syndrome (BWS) and Russell Silver syndrome (RS) are growth disorders with opposing epimutations affecting the H19/IGF2 imprinting center at 11p15.5. Overgrowth and tumor risk in BWS is caused by aberrant expression of the paternally expressed, imprinted IGF2 gene, occurring as a consequence of mosaic hypermethylation within the imprinting center, or to mosaic paternal uniparental disomy (UPD). RS is characterized by severe intrauterine growth retardation (IUGR). A subset of RS cases were recently shown to have mosaic hypomethylation within the H19/IGF2 imprinting center, predicted to silence paternally expressed IGF2 in early development. Molecular diagnosis for BWS and RS involves methylation analysis of the H19 locus, enabling discrimination of allelic methylation patterns. In this study, methylation-sensitive high-resolution melting analysis (MS-HRM) was used to analyze methylation within the intergenic region of the H19 locus. A total of 36 samples comprising normal control (11), BWS (19), and RS (six) DNA were analyzed in a blinded study and scored as hypermethylated, normal, or hypomethylated. Results were compared with those derived by methylation-sensitive Southern blotting using the restriction enzymes Rsa I and Hpa II. A total of 100% concordance was obtained for the Southern blotting and MS-HRM scores. A total of three samples with paternal duplication affecting the H19/IGF2 region were scored as equivocal by both methods; however, 33 out of 36 (92%) the samples were unambiguously scored as being hypermethylated, hypomethylated, or normally methylated using MS-HRM. We conclude that MS-HRM is a rapid, cost-effective, and sensitive method for screening mosaic methylation changes at the H19 locus in BWS and RS. Hum Mutat 0,1,6, 2008. © 2008 Wiley-Liss, Inc. [source] Imprinting centers, chromatin structure, and diseaseJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Hidenobu Soejima Abstract Two regions that best exemplify the role of genetic imprinting in human disease are the Prader,Willi syndrome/Angelman syndrome (PWS/AS) region in 15q11-q13 and the Beckwith,Wiedemann syndrome (BWS) region in 11p15.5. In both regions, cis-acting sequences known as imprinting centers (ICs) regulate parent-specific gene expression bidirectionally over long distances. ICs for both regions are subject to parent-specific epigenetic marking by covalent modification of DNA and histones. In this review, we summarize our current understanding of IC function and IC modification in these two regions. © 2005 Wiley-Liss, Inc. [source] Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?,PEDIATRIC BLOOD & CANCER, Issue 6 2006Stefan Aretz MD Abstract Background Hepatoblastoma (HB) is the most frequent liver tumor in childhood, occurring in the first few years of life. Surgery combined with chemotherapy has resulted in dramatic improvements in prognosis. However, even today, about one quarter of affected children do not survive the disease. Compared to the general population, the risk of HB is 750,7,500 times higher in children predisposed to familial adenomatous polyposis (FAP), an autosomal-dominant cancer predispostion syndrome caused by germline mutations in the tumor suppressor gene APC. Only limited data exist about the frequency of APC germline mutations in cases of apparently sporadic HB without a family history of FAP. Procedure In our sample of 1,166 German FAP families, all known cases of HB were registered. In addition, 50 patients with apparently sporadic HB were examined for APC germline mutations. Results In the FAP families, seven unrelated cases of HB are documented; three had been detected at an advanced stage. In patients with apparently sporadic HB, germline mutations in the APC gene were identified in 10%. Conclusions These data raise the issue of the appropriate screening for HB in children of FAP patients. To date, the efficiency of surveillance for HB is unclear. In Beckwith,Wiedemann syndrome (BWS), recent studies suggest an earlier detection of both Wilms tumor and HB by frequent screening. We discuss the rationale and implications of a screening program; besides the examination procedure itself, screening for HB in children of FAP patients would have important consequences for the policy of predictive testing in FAP. In a substantial fraction of sporadic HB, the disease is obviously the first manifestation of a de novo FAP. These patients should be identified by routine APC mutation screening and undergo colorectal surveillance thereafter. Pediatric Blood Cancer 2006;47:811,818. © 2005 Wiley-Liss, Inc. [source] Familial Beckwith,Wiedemann syndrome due to CDKN1C mutation manifesting with recurring omphalocelePRENATAL DIAGNOSIS, Issue 5 2008Antonio Percesepe No abstract is available for this article. [source] Placental mesenchymal dysplasia associated with fetal aneuploidyPRENATAL DIAGNOSIS, Issue 3 2005Marta C. Cohen Abstract Objectives To describe three cases of placental mesenchymal dysplasia (PMD) associated with abnormal karyotype and review the cases reported in the literature. Methods The cases were retrieved from the files of three different institutions. A search of the English language literature was performed using Medline database. Results Placental abnormalities suggestive of molar changes were seen on the prenatal ultrasound scans. Histologically, the cases had large, hydropic stem villi with myxomatous stroma, cistern formation and ,chorangiomatoid' changes. The placental and fetal karyotypes identified were trisomy 13 (47,XX,t(1:13)(q32;q32)+ 13); Klinefelter syndrome (47,XXY) and triploidy (69,XXX). Including these 3 cases, of 66 reported cases, 51 (78%) were female and 14 (22%) male (ratio 3.6:1); the karyotype was normal in 32/36 (89%) and abnormal in 4/36 (11%); Beckwith,Wiedemann syndrome was confirmed or suspected in 15/66 (23%). Excluding termination of pregnancies, intrauterine death occurred in 18/54 (33%) cases. Conclusion Molar ultrasonographic appearances associated with increased maternal serum alpha-fetoprotein but normal, or slightly elevated, levels of ß human Chorionic Gonadotrophin should raise the clinical suspicion of PMD. The diagnosis of this condition should not be disregarded when an abnormal fetus and/or an abnormal karyotype are demonstrated. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||