title: CNV analysis in 169 patients with bladder exstrophy-epispadias complex.
abstract: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology.
  
  
  
  To detect further CNVs, array analysis was performed in 169 BEEC patients. Prior to inclusion, 22q11.21 duplications were excluded using multiplex ligation-dependent probe amplification.
  
  
  
  Following the application of stringent filter criteria, seven rare CNVs were identified: n = 4, not present in 1307 in-house controls; n = 3, frequency of <0.002 in controls. These CNVs ranged from 1 to 6.08 Mb in size. To identify smaller CNVs, relaxed filter criteria used in the detection of previously reported BEEC associated chromosomal regions were applied. This resulted in the identification of six additional rare CNVs: n = 4, not present in 1307 in-house controls; n = 2, frequency <0.0008 in controls. These CNVs ranged from 0.03-0.08 Mb in size. For 10 of these 13 CNVs, confirmation and segregation analyses were performed (5 of maternal origin; 5 of paternal origin). Interestingly, one female with classic bladder extrophy carried a 1.18 Mb duplication of 22q11.1, a chromosomal region that is associated with cat eye syndrome.
  
  
  
  A number of rare CNVs were identified in BEEC patients, and these represent candidates for further evaluation. Rare inherited CNVs may constitute modifiers of, or contributors to, multifactorial BEEC phenotypes.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: von Lowtzow
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, Bonn, Germany.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Marsch
authors.affiliation: Department of Urology and Pediatric Urology, Ulm, Germany.
authors.forename: Anne-Karoline
authors.initials: AK
authors.lastname: Ebert
authors.affiliation: Department of Pediatric Urology, St. Hedwig Hospital Barmherzige Brüder, Regensburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rösch
authors.affiliation: Department of Pediatric and Adolescent Urology, University of Mannheim, Mannheim, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Stein
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, Children's Hospital of Cologne, Cologne, Germany.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Boemers
authors.affiliation: Department of Urology, Division of Pediatric Urology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Hirsch
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Carlo
authors.initials: C
authors.lastname: Marcelis
authors.affiliation: Pediatric Urology Center, Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Wouter F J
authors.initials: WF
authors.lastname: Feitz
authors.affiliation: Department of Medical Sciences and Medical Genetics Unit, Città della Salute e della Scienza University Hospital, University of Torino, Torino, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Brusco
authors.affiliation: Department of Medical Sciences and Medical Genetics Unit, Città della Salute e della Scienza University Hospital, University of Torino, Torino, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Migone
authors.affiliation: Institute for Maternal and Child Health, IRCCS Burlo Garofalo, Trieste, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Grazia
authors.affiliation: Institute of Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Neonatology and Pediatric Intensive Care, University of Bonn, Bonn, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.affiliation: Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, Bonn, D-53127, Germany. mludwig@uni-bonn.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life & Brain Center, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
mesh_terms: D000782:Aneuploidy; D001746:Bladder Exstrophy / Q000235:genetics*; D025063:Chromosome Disorders / Q000235:genetics; D058674:Chromosome Duplication; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D020732:Cytogenetic Analysis / Q000379:methods*; D056915:DNA Copy Number Variations; D005124:Eye Abnormalities / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D000072741:Maternal Inheritance; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D000072740:Paternal Inheritance
keywords: Bladder exstrophy-epispadias complex; Copy number variation; EFNB1; Genetic testing