1881 COMPARATIVE GENOMIC HYBRIDIZATION MICROARRAY IDENTIFIES UNRECOGNIZED STRUCTURAL CHROMOSOMAL DEFECTS IN MEN WITH NONOBSTRUCTIVE AZOOSPERMIA

Abstract

You have accessJournal of UrologyInfertility: Physiology, Pathophysiology, Basic Research1 Apr 20101881 COMPARATIVE GENOMIC HYBRIDIZATION MICROARRAY IDENTIFIES UNRECOGNIZED STRUCTURAL CHROMOSOMAL DEFECTS IN MEN WITH NONOBSTRUCTIVE AZOOSPERMIA Carolina J. Jorgez, John W. Weedin, Kathleen Hwang, Larry I. Lipshultz, and Dolores J. Lamb Carolina J. JorgezCarolina J. Jorgez More articles by this author , John W. WeedinJohn W. Weedin More articles by this author , Kathleen HwangKathleen Hwang More articles by this author , Larry I. LipshultzLarry I. Lipshultz More articles by this author , and Dolores J. LambDolores J. Lamb More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1834AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Known genetic abnormalities account for 15-20% of male infertility. However, an estimated 50% of male factor infertility may be caused or contributed by genetic influences. We evaluated comparative genomic hybridization microarray (aCGH) as a tool to identify regions of chromosome duplication or deletion in men with nonobstructive azoospermia (NOA) that are too small to be detected on a routine karyotype. METHODS 2 fertile and 10 NOA men were analyzed by aCGH using 135K, 385K, and 720K NimbleGen arrays (Roche). The results were analyzed with Nexus Copy Number software (BioDiscovery) and SignalMap (Roche). These high-resolution arrays span most of the genome, allowing the detection of submicroscopic chromosomal defects. This resolution allows identification of break-points of each duplication or deletion. Each suspected chromosomal gain or loss was validated by QPCR copy number variant Taqman-assays (ABI) or FISH. Prior to aCGH analysis, each male with NOA underwent a comprehensive evaluation for male factor infertility, including PCR for Y-chromosome microdeletions and routine karyotype. RESULTS In 90% of men with NOA, chromosome duplications or deletions in 13 distinct regions were identified (1p12, 1q32, 6p25, 6q22, 7p14, 9q32, 11q13, 14q22, 14q32, 15q15, 19p13, 20q11, Xp22). 9 of these regions lacked copy number variants, and encode genes that are highly expressed in the testis. None of these regions of chromosome gain or loss were identified by the karyotype. Other candidate regions were also identified. In 3 men presenting with Y-chromosome microdeletions, a gain in Xp22 was observed along with duplication of the SHOX gene, a gene implicated in determining human height. Mean height was 54.5 inches (range 53-56). Mean testis volume was 8.7 mL (range 4-12), mean FSH was 44 mIU/mL (range 27-72), and mean testosterone was 256 ng/dL (range 231-291). CONCLUSIONS aCGH has the potential to identify duplications and deletions in submicroscopic chromosomal regions that are unrecognized by routine karyotype. Additional genes involved in male reproduction may be identified by aCGH analysis, and could be important in diagnosis, counseling, and treatment in men with NOA. Houston, TX© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e731 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carolina J. Jorgez More articles by this author John W. Weedin More articles by this author Kathleen Hwang More articles by this author Larry I. Lipshultz More articles by this author Dolores J. Lamb More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...