CNV analysis in 169 patients with bladder exstrophy-epispadias complex

Language
en
Document Type
Article
Issue Date
2016-12-30
Issue Year
2016
Authors
von Lowtzow, Catharina
Hofmann, Andrea
Zhang, Rong
Marsch, Florian
Ebert, Anne-Karoline
Rösch, Wolfgang
Stein, Raimund
Boemers, Thomas M.
Hirsch, Karin
Marcelis, Carlo
Editor
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.

Journal Title
BMC Medical Genetics
Volume
17
Citation
BMC Medical Genetics 17 (2016). <http://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-016-0299-x>
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