Abstract
BackgroundThe 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.MethodsTo 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.ResultsFollowing 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.ConclusionsA 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.
Highlights
The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum
The phenotype ranges from epispadias (E) and classic bladder exstrophy (CBE), to the most severe form, cloacal exstrophy (CE)
Examination of copy number variation (CNV) of
Summary
The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. The phenotype ranges from epispadias (E) and classic bladder exstrophy (CBE), to the most severe form, cloacal exstrophy (CE) The latter is often referred to as the OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects) [1,2,3]. Extensive recent research has implicated both inherited and de novo genetic factors in BEEC etiology These factors include common single nucleotide polymorphisms (SNPs) [10, 11] and rare larger genomic aberrations, such as chromosomal aberrations and copy number variations (CNVs) (Table 1 [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]). Genetic von Lowtzow et al BMC Medical Genetics (2016) 17:35
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