Unbalanced segregation of a paternal t(9;11)(p24.3;p15.4) translocation causing familial Beckwith-Wiedemann syndrome: a case report.

BACKGROUND: The vast majority of cases with Beckwith-Wiedemann syndrome (BWS) are caused by a molecular defect in the imprinted chromosome region 11p15.5. The underlying mechanisms include epimutations, uniparental disomy, copy number variations, and structural rearrangements. In addition, maternal loss-of-function mutations in CDKN1C are found. Despite growing knowledge on BWS pathogenesis, up to 20% of patients with BWS phenotype remain without molecular diagnosis. CASE PRESENTATION: Herein, we report an Iranian family with two females affected with BWS in different generations. Bisulfite pyrosequencing revealed hypermethylation of the H19/IGF2: intergenic differentially methylated region (IG DMR), also known as imprinting center 1 (IC1) and hypomethylation of the KCNQ1OT1: transcriptional start site (TSS) DMR (IC2). Array CGH demonstrated an 8 Mb duplication on chromosome 11p15.5p15.4 (205,827-8,150,933) and a 1 Mb deletion on chromosome 9p24.3 (209,020-1,288,114). Chromosome painting revealed that this duplication-deficiency in both patients is due to unbalanced segregation of a paternal reciprocal t(9;11)(p24.3;p15.4) translocation. CONCLUSIONS: This is the first report of a paternally inherited unbalanced translocation between the chromosome 9 and 11 short arms underlying familial BWS. Copy number variations involving the 11p15.5 region are detected by the consensus diagnostic algorithm. However, in complex cases which do not only affect the BWS region itself, characterization of submicroscopic chromosome rearrangements can assist to estimate the recurrence risk and possible phenotypic outcomes

Down-regulation of TGF-β, VEGF, and bFGF in vascular endothelial cells of chicken induced by a brittle star (Ophiocoma erinaceus) extract

Cell biology; Pharmaceutical science; Molecular biology; Cancer research; Ophiocoma erinaceus; Vascular endothelial growth factor; Chorioallantoic membrane; Angiogenesis inhibitors; Hyperplasia © 2020 Great attention has been focused on the discovery of anti-angiogenic natural and synthetic compounds to be finally used as or at least a part of the treatment of tumors. The marine ecosystems provide diversity in natural chemicals with the potential of being exploited as medicines in the treatment of diseases. Several studies have investigated Ophiuroids as a source of anti-tumor and anti-metastatic organisms. Here, we described the inhibitory effects of an ethanolic crude extract of brittle star (Ophiocoma erinaceus) on angiogenesis and the expression level of TGF-β, VEGF, and bFGF in chicken chorioallantoic membrane (CAM) as an experimental model. To do this 45 embryonated eggs were randomly divided into six groups including the control group, sham, three experimental groups and positive. The number and the length of vessels were calculated using ImageJ® software. The relative mRNA levels of the genes in different groups were evaluated by qRT-PCR method. Our study was suggestive of an anti-angiogenesis effect of brittle star ethanolic crude extract in a CAM model. The extract also showed a pharmacological effect of down-regulation of mRNA related to VEGF, TGF-β, and bFGF genes on chicken vascular endothelial cells. It was also showed that the observed inhibitory effect is with a dose-dependent manner in which the highest inhibitory effect belonged to the highest used dose. We indicated the anti-angiogenesis properties of the Persian Gulf brittle star. Further studies are needed in other aspects of the brittle star extract in the treatment of angiogenesis, hyperplasia, and cancers. © 202