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. 2016 Apr 30;17(1):35.
doi: 10.1186/s12881-016-0299-x.

CNV analysis in 169 patients with bladder exstrophy-epispadias complex

Catharina von Lowtzow  1 , Andrea Hofmann  1   2 , Rong Zhang  1   2 , Florian Marsch  1 , Anne-Karoline Ebert  3 , Wolfgang Rösch  4 , Raimund Stein  5 , Thomas M Boemers  6 , Karin Hirsch  7 , Carlo Marcelis  8 , Wouter F J Feitz  9 , Alfredo Brusco  10 , Nicola Migone  10 , Massimo Di Grazia  11 , Susanne Moebus  12 , Markus M Nöthen  1   2 , Heiko Reutter  1   13 , Michael Ludwig  14 , Markus Draaken  1   2
Affiliations

CNV analysis in 169 patients with bladder exstrophy-epispadias complex

Catharina von Lowtzow et al. BMC Med Genet. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Bladder exstrophy-epispadias complex; Copy number variation; EFNB1; Genetic testing.

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Figures

Fig. 1
Fig. 1
Results of molecular karyotyping: (Top) Chromosome 22q11.1 duplication comprising 34 markers (boxed), observed in a CBE female as compared to those described in an earlier report [42] and listed in the DECIPHER database. (Bottom) RefSeq genes (according to hg19) located in the duplicated region
See this image and copyright information in PMC

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