CNV analysis in 169 patients with bladder exstrophy-epispadias complex

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Bladder Exstrophy / genetics*
  • Chromosome Disorders / genetics
  • Chromosome Duplication
  • Chromosomes, Human, Pair 22 / genetics
  • Cytogenetic Analysis / methods*
  • DNA Copy Number Variations*
  • Eye Abnormalities / genetics
  • Female
  • Humans
  • Male
  • Maternal Inheritance
  • Oligonucleotide Array Sequence Analysis / methods*
  • Paternal Inheritance

Supplementary concepts

  • Schmid-Fraccaro syndrome