Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1

Carolina J. Jorgez, Jill A. Rosenfeld, Nathan R. Wilken, Hima V. Vangapandu, Aysegul Sahin, Dung Pham, Claudia M.B. Carvalho, Anne Bandholz, Amanda Miller, David D. Weaver, Barbara Burton, Deepti Babu, John S. Bamforth, Timothy Wilks, Daniel P. Flynn, Elizabeth Roeder, Ankita Patel, Sau W. Cheung, James R. Lupski, Dolores J. Lamb

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Normal development of the genitourinary (GU) tract is a complex process that frequently goes awry. In male children the most frequent congenital GU anomalies are cryptorchidism (1-4%), hypospadias (1%) and micropenis (0.35%). Bladder exstrophy and epispadias complex (BEEC) (1:47000) occurs less frequently but significantly impacts patients' lives. Array comparative genomic hybridization (aCGH) identified seven individuals with overlapping deletions in the 2p15 region (66.0 kb-5.6 Mb). Six of these patients have GU defects, while the remaining patient has no GU defect. These deletions encompass the transcription factor OTX1. Subjects 2-7 had large de novo CNVs (2.39-6.31 Mb) and exhibited features similar to those associated with the 2p15p16.1 and 2p15p14 microdeletion syndromes, including developmental delay, short stature, and variable GU defects. Subject-1 with BEEC had the smallest deletion (66 kb), which deleted only one copy of OTX1. Otx1-null mice have seizures, prepubescent transient growth retardation and gonadal defects. Two subjects have short stature, two have seizures, and six have GU defects, mainly affecting the external genitalia. The presence of GU defects in six patients in our cohort and eight of thirteen patients reported with deletions within 2p14p16.1 (two with deletion of OTX1) suggest that genes in 2p15 are important for GU development. Genitalia defects in these patients could result from the effect of OTX1 on pituitary hormone secretion or on the regulation of SHH signaling, which is crucial for development of the bladder and genitalia.

Original languageEnglish (US)
Article numbere107028
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1'. Together they form a unique fingerprint.

  • Cite this

    Jorgez, C. J., Rosenfeld, J. A., Wilken, N. R., Vangapandu, H. V., Sahin, A., Pham, D., Carvalho, C. M. B., Bandholz, A., Miller, A., Weaver, D. D., Burton, B., Babu, D., Bamforth, J. S., Wilks, T., Flynn, D. P., Roeder, E., Patel, A., Cheung, S. W., Lupski, J. R., & Lamb, D. J. (2014). Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1. PloS one, 9(9), [e107028]. https://doi.org/10.1371/journal.pone.0107028