@article {8352, title = {CNV analysis in 169 patients with bladder exstrophy-epispadias complex.}, journal = {BMC Med Genet}, volume = {17}, year = {2016}, month = {2016}, pages = {35}, 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.

}, issn = {1471-2350}, doi = {10.1186/s12881-016-0299-x}, author = {von Lowtzow, Catharina and Hofmann, Andrea and Zhang, Rong and Marsch, Florian and Ebert, Anne-Karoline and R{\"o}sch, Wolfgang and Stein, Raimund and Boemers, Thomas M and Hirsch, Karin and Marcelis, Carlo and Feitz, Wouter F J and Brusco, Alfredo and Migone, Nicola and Di Grazia, Massimo and Moebus, Susanne and N{\"o}then, Markus M and Reutter, Heiko and Ludwig, Michael and Draaken, Markus} }