1616 CHROMOSOME 13Q A SUSCEPTIBILITY LOCUS FOR EPISPADIAS

Abstract

You have accessJournal of UrologyPediatrics: Congenital Anomalies - Lower Urinary Tract & Genitalia II1 Apr 20121616 CHROMOSOME 13Q A SUSCEPTIBILITY LOCUS FOR EPISPADIAS Carolina Jorgez, Shelly Bian, Venkata Vangapandu, Aysegul Sahin, and Dolores Lamb Carolina JorgezCarolina Jorgez Houston, TX More articles by this author , Shelly BianShelly Bian Houston, TX More articles by this author , Venkata VangapanduVenkata Vangapandu Houston, TX More articles by this author , Aysegul SahinAysegul Sahin Houston, TX More articles by this author , and Dolores LambDolores Lamb Houston, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1411AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Epispadias is a rare congenital urological defect with an incidence of 1:150.000 characterized by incomplete dorsal tubularization of the urethral plate. Male epispadias is usually diagnosed at birth. In females, however, epispadias may only be diagnosed as a result of persistent incontinence. The majority of cases are sporadic, with a normal karyotype and unknown etiology, though epidemiologic data suggest a strong genetic component. Our aim is to identify candidate genes responsible for epispadias using array comparative genomic hybridization (aCGH). METHODS Genomic DNA from 6 male epispadia patients was analyzed using 3x720K aCGH from NimbleGen. Each copy number variation (CNV) identified by aCGH was validated by using Taqman QPCR. Sanger DNA sequencing of selected genes was performed to identify single nucleotide polymorphisms (SNPs). RESULTS At least one CNV was identified in all patients, with 50% having two CNVs. Of the 9 CNVs identified, 78% were microdeletions that included chromosomal regions (genes) 2p13.1 (NAT8), 2q36.3 (FBX036), 6q15 (RNGTT), 13q14.2 (SUCLA2), 13q32.1 (HS6ST3), 20q11.21 (SNTA1) and 20q13.13 (PTGIS). Microduplications were observed at 8q22.1 (UQCRB) and 13q21.32 (PCDH9). CNV inheritance occurred in 44% of the cases. Interestingly, a microdeletion involving SUCLA2 and a microduplication involving PCDH9 were observed in two brothers, one with epispadias and the other with hypospadias. Of note, both genes are located in chromosomal region 13q. The CNV in SUCLA2 was paternally inherited, and 2 SNPs, 37L®W and 143K®K, were identified with maternal inheritance. Their normal sister did not inherit either the CNVs or the SNPs. SUCLA2 is a mitochondrial enzyme expressed in several mouse and human tissues including kidney and muscle. We found SUCLA2 expressed in the embryonic urethra and ureter. CONCLUSIONS Nine new CNV regions were identified in men with epispadias with 33% of these located on chromosome 13q that include SUCLA2 a promising candidate. SUCLA2 mutations result in respiratory chain complex I disease, which is associated with a mitochondrial DNA depletion syndrome involving hypotonia, muscular atrophy, and in few cases hypospadias. Likewise, a defect in TMEM70, another mitochondrial enzyme, results in respiratory chain complex V disease with cardiomyopathy and hypospadias present in the majority of the cases. These data suggest that mitochondrial genes may play a role in the GU tract development. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e653-e654 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carolina Jorgez Houston, TX More articles by this author Shelly Bian Houston, TX More articles by this author Venkata Vangapandu Houston, TX More articles by this author Aysegul Sahin Houston, TX More articles by this author Dolores Lamb Houston, TX More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...