• PMID: 25203062
• Gene Name: OTX1
• Condition: Genitourinary defects
• Association: Six of these patients have GU defects, while the remaining patient has no GU defect
• Population size: 7
• Population details: 7 individuals with overlapping deletions in the 2p15 region
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Genitourinary defects

Genitourinary defects associated with genomic deletions in 2p15 encompassing OTX1

Jorgez CJ, Rosenfeld JA, Wilken NR, Vangapandu HV, Sahin A, Pham D, Carvalho CM, Bandholz A, Miller A, Weaver DD, Burton B, Babu D, Bamforth JS, Wilks T, Flynn DP, Roeder E, Patel A, Cheung SW, Lupski JR, Lamb DJ.

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. FAU - Jorgez, Carolina J AU - Jorgez CJ AD - Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas, United States of America; Scott Department of Urology, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Rosenfeld, Jill A AU - Rosenfeld JA AD - Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington, United States of America. FAU - Wilken, Nathan R AU - Wilken NR AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Vangapandu, Hima V AU - Vangapandu HV AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Sahin, Aysegul AU - Sahin A AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Pham, Dung AU - Pham D AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Carvalho, Claudia M B AU - Carvalho CM AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Bandholz, Anne AU - Bandholz A AD - Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington, United States of America. FAU - Miller, Amanda AU - Miller A AD - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America. FAU - Weaver, David D AU - Weaver DD AD - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America. FAU - Burton, Barbara AU - Burton B AD - Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States of America. FAU - Babu, Deepti AU - Babu D AD - University of Alberta, Edmonton, Alberta, Canada. FAU - Bamforth, John S AU - Bamforth JS AD - University of Alberta, Edmonton, Alberta, Canada. FAU - Wilks, Timothy AU - Wilks T AD - Madigan Army Medical Center, Department of Pediatrics, Tacoma, Washington, United States of America. FAU - Flynn, Daniel P AU - Flynn DP AD - Department of Children's Endocrinology, St. Luke's Children's Specialty Center, Boise, Idaho, United States of America. FAU - Roeder, Elizabeth AU - Roeder E AD - Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America. FAU - Patel, Ankita AU - Patel A AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Cheung, Sau W AU - Cheung SW AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America. FAU - Lupski, James R AU - Lupski JR AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.