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Journal Article

Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12.

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50465

Pennimpede,  Tracie
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons73893

Wolter,  Stefanie
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons16043

Wittler,  Lars
Research Group of Developmental Biology, MPI for biophysical chemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50201

Herrmann,  Bernhard G.
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Draaken, M., Mughal, S. S., Pennimpede, T., Wolter, S., Wittler, L., Ebert, A.-K., et al. (2013). Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12. Birth Defects Research, Part A: Clinical and Molecular Teratology, 97(3), 133-139. doi:10.1002/bdra.23112.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-EA0A-C
Abstract
The exstrophy-epispadias complex (BEEC) is a urogenital birth defect of varying severity. The causes of the BEEC are likely to be heterogeneous, with individual environmental or genetic risk factors still being largely unknown. In this study, we aimed to identify de novo causative copy number variations (CNVs) that contribute to the BEEC. METHODS Array-based molecular karyotyping was performed to screen 110 individuals with BEEC. Promising CNVs were tested for de novo occurrence by investigating parental DNAs. Genes located in regions of rearrangements were prioritized through expression analysis in mice to be sequenced in the complete cohort, to identify high-penetrance mutations involving small sequence changes. RESULTS A de novo 0.9 Mb microduplication involving chromosomal region 19p13.12 was identified in a single patient. This region harbors 20 validated RefSeq genes, and in situ hybridization data showed specific expression of the Wiz gene in regions surrounding the cloaca and the rectum between GD 9.5 and 13.5. Sanger sequencing of the complete cohort did not reveal any pathogenic alterations affecting the coding region of WIZ. CONCLUSIONS The present study suggests chromosomal region 19p13.12 as possibly involved in the development of CBE, but further studies are needed to prove a causal relation. The spatiotemporal expression patterns determined for the genes encompassed suggest a role for Wiz in the development of the phenotype. Our mutation screening, however, could not confirm that WIZ mutations are a frequent cause of CBE, although rare mutations might be detectable in larger patient samples.