{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:22:03Z","timestamp":1784042523802,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T00:00:00Z","timestamp":1632096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BONFOR Forschungskommission, Medical Faculty of the University of Bonn","award":["O-149.0128"],"award-info":[{"award-number":["O-149.0128"]}]},{"name":"BONFOR Forschungskommission, Medical Faculty of the University of Bonn","award":["O-149.0123"],"award-info":[{"award-number":["O-149.0123"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE 275 1723\/1-3"],"award-info":[{"award-number":["RE 275 1723\/1-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE 1723\/4-1"],"award-info":[{"award-number":["RE 1723\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.<\/jats:p>","DOI":"10.3390\/genes12091449","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"1449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO)"],"prefix":"10.3390","volume":"12","author":[{"given":"Luca M.","family":"Schierbaum","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4872-0093","authenticated-orcid":false,"given":"Sophia","family":"Schneider","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2786-8200","authenticated-orcid":false,"given":"Stefan","family":"Herms","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany"},{"name":"Human Genomics Research Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5239-5137","authenticated-orcid":false,"given":"Sugirthan","family":"Sivalingam","sequence":"additional","affiliation":[{"name":"Institute for Medical Biometry, Informatics and Epidemiology, Medical Faculty, University of Bonn, 53127 Bonn, Germany"},{"name":"Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, 53127 Bonn, Germany"},{"name":"Core Unit for Bioinformatics Data Analysis, Medical Faculty, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Fabian","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3591-5265","authenticated-orcid":false,"given":"Heiko","family":"Reutter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany"},{"name":"Department of Neonatology and Pediatric Intensive Care, University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Marburg, 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waltraut M.","family":"Merz","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Prenatal Medicine, University of Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1753-7560","authenticated-orcid":false,"given":"Marcin","family":"Tkaczyk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Immunology and Nephrology, Polish Mother\u2019s Memorial Hospital Research Institute of Lodz, 93-428 \u0141\u00f3d\u017a, Poland"},{"name":"Department of Pediatrics, Cardiology and Immunology, Medical University of \u0141\u00f3d\u017a, 93-428 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0776-4946","authenticated-orcid":false,"given":"Monika","family":"Miklaszewska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, 31-007 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5698-6863","authenticated-orcid":false,"given":"Przemyslaw","family":"Sikora","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Szmigielska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Nephrology, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazyna","family":"Krzemien","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Nephrology, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Zachwieja","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, 31-007 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-261X","authenticated-orcid":false,"given":"Maria","family":"Szczepanska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8762-8866","authenticated-orcid":false,"given":"Katarzyna","family":"Taranta-Janusz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Nephrology, Medical University of Bia\u0142ystok, 15-089 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4903-5477","authenticated-orcid":false,"given":"Pawel","family":"Kroll","sequence":"additional","affiliation":[{"name":"Neurourology Unit, Pediatric Surgery and Urology Clinic, 61-701 Pozna\u0144, Poland"},{"name":"Neurourology Unit, Poznan University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1235-563X","authenticated-orcid":false,"given":"Marcin","family":"Polok","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology, University of Zielona G\u00f3ra, 65-417 Zielona G\u00f3ra, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Zaniew","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Zielona G\u00f3ra, 65-417 Zielona G\u00f3ra, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-7584","authenticated-orcid":false,"given":"Alina C.","family":"Hilger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Hospital of Bonn, 53127 Bonn, Germany"},{"name":"Department of Neonatology and Pediatric Intensive Care, University Hospital Erlangen, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.1464-410X.1969.tb09967.x","article-title":"Congenital diaphragmatic obstruction of the male posterior urethra","volume":"41","author":"Robertson","year":"1969","journal-title":"Br. J. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bpobgyn.2019.01.003","article-title":"Congenityl urinary tract obstrucion","volume":"58","author":"Cheung","year":"2019","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.earlhumdev.2011.07.004","article-title":"Long-term renal and neurodevelopmental outcome in infants with LUTO, with and without fetal intervention","volume":"87","author":"Morris","year":"2011","journal-title":"Early Hum. Dev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1111\/j.1471-0528.2012.03476.x","article-title":"Congenital lower urinary tract obstruction: A population-based epidemiological study","volume":"119","author":"Malin","year":"2012","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1055\/s-0034-1367042","article-title":"Lower urinary tract obstruction (LUTO)\u2014Clinical picture, prenatal diagnostics and therapeutic options","volume":"218","author":"Bildau","year":"2014","journal-title":"Z. Geburtshilfe Neonatol."},{"key":"ref_6","first-page":"112","article-title":"Renal outcomes of neonates with early presentation of posterior urethral valves: A 10-year single center experience","volume":"40","author":"Coquillette","year":"2020","journal-title":"J. Perinatol. Off. J. Calif. Perinat Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.ajhg.2019.03.023","article-title":"Rare Variants in BNC2 Are Implicated in Autosomal-Dominant Congenital Lower Urinary-Tract Obstruction","volume":"104","author":"Kolvenbach","year":"2019","journal-title":"Am. J. Hum. 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