Clinical and genetic analysis of two cases of Prader-Willi syndrome / 中国综合临床

Objective:To investigate the clinical and genetic characteristics of Prader-Willi syndrome (PWS).Methods:The clinical data and genetic characteristics of 2 children with PWS diagnosed in Hebei Provincial People's Hospital were retrospectively analyzed, and the relevant literature was reviewed.Results:Case 1, male, aged 6 years and 3 months, was presented to the hospital because of short stature, mild mental retardation, dysarthria, scoliosis, cryptorchidism, micropenis, long skull, narrow face, almond eyes, small mouth, thin upper lip, downward corners of the mouth, fair skin. He had hypotonia and feeding difficulties in infancy, and gradually became hyperappetitive. Bilateral cryptorchidism surgery was performed at 1.5 years old, but the effect was not good. Case 2, male, aged 4 years, presented to the hospital mainly due to obesity, hyperappetite, excessive weight gain, backward language and cognitive function, dysarthria, and scoliosis.The infant had feeding difficulties in the early stage, and bilateral cryptorchidism surgery at the age of 2 was not effective.Methylation specific polymerase chain reaction and methylation specific multilink probe amplification were used to detect the loss of the parent fragment in the key region (15q11-13) of PWS, which confirmed Prader-Willi syndrome.Conclusion:PWS is a rare hereditary disease with complex and diverse clinical manifestations and different characteristics in different age groups. It is highly susceptible to unexplained hypotonia and feeding difficulties in infancy. Children with short stature and obesity should be alert to the disease, which can be clearly diagnosed by molecular genetic techniques.

Trofoblasto, impronta y conflicto genómico en gineco-obstetricia / Trophoblast, imprinting and genomic conflict in gynecology-obstetrics

La teoría del Conflicto Genómico es parte de la biología evolutiva y actúa en los mamíferos a través del mecanismo de impronta genética, estos genes cumplen un rol central en el desarrollo fetal y del trofoblasto contribuyendo a un balance entre los requerimientos nutricionales fetales (genes con impronta paterna) y el aporte materno (genes con impronta materna). El desbalance de estos genes tiene implicancias en la etiopatogenia de diversas patologías en Gineco-Obstetricia: en Medicina Fetal (preeclampsia, diabetes gestacional, síndrome de Beckwith-Wiedemann), oncología (mola completa, mola incompleta, teratomas) y fertilidad. Se presenta un caso de displasia mesenquimática placentaria asociado a Beckwith-Wiedemann.

The theory of Genomic Conflict is part of evolutionary biology and acts in mammals through the mechanism of genetic imprinting, these genes play a central role in fetal and trophoblastic development producing a balance between fetal nutritional requirements (genes with paternal imprinting) and maternal supply (genes with maternal imprinting). The imbalance of these genes has implications in the pathogenesis of various diseases in Obstetrics and Gynecology: in Fetal Medicine (preeclampsia, gestational diabetes, Beckwith-Wiedemann syndrome), oncology (complete and partial hydatiform mole, teratomas) and fertility. A case of placental mesenchymal dysplasia associated with Beckwith-Wiedemann is presented.

A patogênese genética e molecular da síndrome de Angelman / The genetic and molecular pathogenesis of the Angelman syndrome

Objetivo: Fornecer uma revisão atualizada em língua portuguesa sobre a síndrome de Angelman, com ênfase nos mecanismos genéticos e moleculares dessa patologia, uma causa de deficiência mental severa que em alguns casos pode apresentar recorrência familiar. Método: Foi feita uma revisão bibliográfica utilizando a base de dados do PubMed, tendo como critérios de busca o termo "Angelman syndrome" isoladamente e combinado com "UBE3A", "clinical", "genetics" e "molecular" no título dos artigos. Dentre esses, foram selecionados artigos de revisão e artigos originais sobre a fisiopatologia da síndrome, com ênfase nos últimos dez anos. Resultados: Utilizando-se "Angelman syndrome" na busca, apareceram cerca de 1.100 artigos, incluindo 240 de revisão. Nos últimos dez anos são mais de 600 artigos, aproximadamente 120 de revisão, 50 por cento dos quais publicados nos últimos cinco anos. Na base de dados SciELO, são apenas nove artigos sobre a síndrome, dos quais três em português e nenhum artigo atual de revisão. Conclusão: Após ter sido uma das principais causas que atraíram atenção ao estudo e ao entendimento dos mecanismos do imprinting genômico, a síndrome de Angelman está agora se revelando como uma patologia das sinapses. Apesar de o entendimento da fisiopatologia molecular da síndrome de Angelman ainda estar longe de ser compreendida, seu estudo está fornecendo uma visão extraordinária sobre os mecanismos que regem a plasticidade sináptica, novamente atraindo a atenção de pesquisadores que trabalham na fronteira do conhecimento.

Objective: The aim of this work is to provide an actualized review in Portuguese language of the main clinical and behavioral features and in particular of the genetic and molecular aspects of Angelman syndrome, a cause of severe intellectual disability, which in rare cases can be recurrent in the family. Method: This paper is a literature review that used as a source of research, scientific papers with the terms "Angelman syndrome" or combined with UBE3A, clinical, genetics, and molecular in their title, retrieved trough the PubMed database. Among those, mainly review articles and original papers about cellular and molecular aspects of the pathology were selected, prioritarily, those published in the last ten years. Results: The term Angelman syndrome retrieved about 1100 papers, including close to 240 review articles. During the last ten years there were over 600 publications, with approximately 120 reviews, 50 percent of whom published in the last five years. The SciELO database was also searched and nine publications about the syndrome were found, three of which in Portuguese and no recent review article. Conclusion: After being one of the main causes to attract attention and stimulate studies to unravel the mechanisms of the genetic imprinting, Angelman syndrome is again in the spotlight because it is revealing itself as pathology of synaptic dysfunction. Albeit still long from understood, the molecular and cellular alterations in Angelman syndrome are allowing an extraordinary insight into the mechanisms which control synaptic plasticity.

Suppressive Effects of Genomic Imprinted Gene PEG10 on Hydrogen Peroxide-induced Apoptosis in L02 Cells / 华中科技大学学报（医学）（英德文版）

The effects of PEG10 on hydrogen peroxide (H2O2)-induced apoptosis in human normal liver cell line L02 were investigated. The PEG10 gene was transfected into L02 cells by lipofectamine,the positive clone was screened by G418 and defined as L02/PEG10,while the cell transfected with empty expression vector (pEGFP-N1) was defined as L02/vector. L02/vector and parental L02 cells served as control. RT-PCR and Western blotting were employed to detect the expression of target genes. H2O2 (50-400 mmol/L) was administered to induce the apoptosis of L02 cells. Cells viability was measured by MTT and the morphological changes of apoptotic cells were determined by fluorescence microscopy using hoechst33342 nuclei staining. DNA fragmentation was observed by agarose gel electrophoresis. PEG10 mRNA and protein levels in L02/PEG10 ceils were significantly increased as compared with those in the control cells. After treatment with 400 mmol/L H2O2 for 24 h,the cellular growth inhibition rate of L02/PEG10 cells was significantly lower (58.2%) than that of L02 (92.5%) and L02/vector (88%). Distinct morphological changes characteristic of cell apoptosis such as karyopyknosis and conglomeration were not observed in L02/PEG10. Ladder-like DNA fragmentation in a dose-dependent manner was observed in both L02 and L02/vector cell lines,but not in L02/PEG10. PEG10 over-expression significantly inhibited cytotoxicity induced by H2O2 on human normal liver cell line L02 by antagonizing H2O2-induced apoptosis.

Study of Genetic Imprinting on 3 Cases of Insulin-Dependent Diabetes Mellitus Developed in Early Infantile Period / 대한소아내분비학회지

Infantile onset diabetes mellitus(especially, neonatal diabetes) is rare disorder and may be transient or permanent. Most patients are full-term but small-for-date infants and typical symptoms occur within the first 4-6 weeks of life, requiring insulin therapy. Neonatal diabetes differs from type 1 diabetes in many aspects and seems to form a distinct entity of inborn pancreatic malfunction. The transient cases often develop type 2 diabetes mellitus later in life. In recent reports, transient neonatal diabetes is associated with paternal uniparental isodisomy and unbalanced duplication of chromosome 6q22-23. In our study, clinical course of case 1 was compatible with transient neonatal diabetes, but chromosomal abnormalities such as above was not shown in DNA analysis. In case 2 and 3, we could not decide exactly on genetic basis.