International journal of pediatrics and child health最新文献

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ETV4 Mutation in a Patient with Congenital Anomalies of the Kidney and Urinary Tract 先天性肾和尿路异常患者的ETV4突变

International journal of pediatrics and child health Pub Date : 2016-09-04 DOI: 10.12974/2311-8687.2016.04.02.1

Jing Chen, A. T. van der Ven, J. Newman, A. Vivante, Nina Mann, H. Aitkenhead, S. Shril, Hadas Ityel, J. Schulz, J. Schmidt, E. Widmeier, O. Gileadi, F. Costantini, Shifaan Thowfeequ, R. Wenger, S. Bauer, R. S. Lee, Weining Lu, Maike Getwan, Michael M. Kaminski, S. Lienkamp, R. Lifton, V. Tasic, E. Kehinde, F. Hildebrandt

{"title":"ETV4 Mutation in a Patient with Congenital Anomalies of the Kidney and Urinary Tract","authors":"Jing Chen, A. T. van der Ven, J. Newman, A. Vivante, Nina Mann, H. Aitkenhead, S. Shril, Hadas Ityel, J. Schulz, J. Schmidt, E. Widmeier, O. Gileadi, F. Costantini, Shifaan Thowfeequ, R. Wenger, S. Bauer, R. S. Lee, Weining Lu, Maike Getwan, Michael M. Kaminski, S. Lienkamp, R. Lifton, V. Tasic, E. Kehinde, F. Hildebrandt","doi":"10.12974/2311-8687.2016.04.02.1","DOIUrl":"https://doi.org/10.12974/2311-8687.2016.04.02.1","url":null,"abstract":"Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common reason for chronic kidney disease in children. Although more than 30 monogenic causes have been implicated in isolated forms of human CAKUT so far, the vast majority remains elusive. To identify novel monogenic causes of CAKUT we applied homozygosity mapping, together with whole exome sequencing, in a patient from consanguineous descent with isolated CAKUT. We identified a homozygous missense mutation (p.Arg415His) of the Ets Translocation Variant Gene 4 (ETV4). The transcription factor ETV4 is a downstream target of the GDNF/RET signaling pathway that plays a crucial role in kidney development. We show by means of electrophoretic mobility shift assay that the Arg415His mutant causes loss of the DNA binding affinity of ETV4 and fails to activate transcription in a cell-based luciferase reporter assay. We furthermore investigated the impact of the mutant protein on cell migration rate. Unlike wildtype ETV4, the Arg415His mutant failed to rescue cell migration defects observed in two ETV4 knock-down cell-lines. We therefore identified and functionally characterized a recessive mutation in ETV4 in a human patient with CAKUT. We hypothesize that the pathomechanism of this mutation could be via loss of the transcriptional function of ETV4, and a resulting abrogation of GDNF/RET/ETV4 signaling pathway. ","PeriodicalId":91713,"journal":{"name":"International journal of pediatrics and child health","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66337112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Recurrent rhinovirus detections in children following a rhinovirus-induced wheezing exacerbation: A retrospective study. 儿童鼻病毒引起的喘息加重后复发性鼻病毒检测:一项回顾性研究。

International journal of pediatrics and child health Pub Date : 2015-08-01 DOI: 10.12974/2311-8687.2015.03.01.2

Sofie Halmø Hürdum, Guicheng Zhang, S. Khoo, Joelene A. Bizzintino, Kimberley Franks, K. Lindsay, A. Keil, D. Cox, J. Goldblatt, Y. Bochkov, J. Gern, C. Ulrik, P. N. Souëf, I. Laing

{"title":"Recurrent rhinovirus detections in children following a rhinovirus-induced wheezing exacerbation: A retrospective study.","authors":"Sofie Halmø Hürdum, Guicheng Zhang, S. Khoo, Joelene A. Bizzintino, Kimberley Franks, K. Lindsay, A. Keil, D. Cox, J. Goldblatt, Y. Bochkov, J. Gern, C. Ulrik, P. N. Souëf, I. Laing","doi":"10.12974/2311-8687.2015.03.01.2","DOIUrl":"https://doi.org/10.12974/2311-8687.2015.03.01.2","url":null,"abstract":"INTRODUCTION\u0000It is unclear if children with a rhinovirus (RV)-induced wheezing exacerbation are more susceptible to viruses longitudinally, and whether a parental history of asthma and/or allergy impacts their susceptibility. The objective of this study was to determine if RV, RV-A and RV-C related wheezing exacerbations in children were associated with prior or subsequent viral detections and investigate the role of parental history of asthma and allergy.\u0000\u0000\u0000MATERIALS AND METHODS\u0000Children presenting to hospital with acute wheeze were prospectively recruited and tested for respiratory viruses. Data on viruses detected in other respiratory samples (May 1997 to December 2012) were collected from hospital microbiology records and additional RV testing was performed on stored hospital respiratory samples (September 2009 to December 2012). A positive parental history was defined as either parent with self-reported asthma and/or allergy.\u0000\u0000\u0000RESULTS\u0000At recruitment, RV was detected in 69.2% of samples from children with an acute wheezing episode (n=373, 0-16 years of age), with RV-C the most common virus (65.5%). Children with a history of parental asthma and/or allergy and RV at recruitment had a 14-fold increased incidence rate ratio (IRR) of subsequent RV detection (IRR 14.0, 95% CI 1.9-104.1; p=0.01) compared with children without RV at recruitment. Children without this parental history had a reduced incident rate ratio for samples assessed during this time (IRR 0.5, 95% CI 0.3-0.9; p=0.03).\u0000\u0000\u0000CONCLUSION\u0000Children with a parental history of asthma and/or allergy may become more susceptible to recurrent symptomatic RV infections.","PeriodicalId":91713,"journal":{"name":"International journal of pediatrics and child health","volume":"3 1 1","pages":"10-18"},"PeriodicalIF":0.0,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66337506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

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