• PMID: 25439843
• Gene Name: E2F1
• Condition: Nonobstructive azoospermia (NOA)
• Association: E2F1 microduplications or microdeletions are present in men with NOA (7.3%). Duplications or deletions of E2F1occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset
• Population size: 188
• Population details: 188 (110 with NOA, 78 fertile controls.)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Nonobstructive azoospermia (NOA)

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia

Jorgez CJ, Wilken N, Addai JB, Newberg J, Vangapandu HV, Pastuszak AW, Mukherjee S, Rosenfeld JA, Lipshultz LI, Lamb DJ.

OBJECTIVE: To identify gene dosage changes associated with nonobstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH). DESIGN: Prospective study. SETTING: Medical school. PATIENT(S): One hundred ten men with NOA and 78 fertile controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy number variations (CNVs); Taqman CNV assays to validate CNVs; mutation identification by Sanger sequencing; and histological analyses of testicular tissues. RESULT(S): A microduplication at 20q11.22 encompassing E2F transcription factor-1 (E2F1) was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and in an additional 102 men with NOA screened using Taqman CNV assays, for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls. CONCLUSION(S): E2F1 microduplications or microdeletions are present in men with NOA (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or overexpressing E2f1. CI - Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Jorgez, Carolina J AU - Jorgez CJ AD - Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas. Electronic address: cj129804@bcm.edu. FAU - Wilken, Nathan AU - Wilken N AD - Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas. FAU - Addai, Josephine B AU - Addai JB AD - Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas. FAU - Newberg, Justin AU - Newberg J AD - Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas. FAU - Vangapandu, Hima V AU - Vangapandu HV AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas. FAU - Pastuszak, Alexander W AU - Pastuszak AW AD - Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas. FAU - Mukherjee, Sarmistha AU - Mukherjee S AD - Scott Department of Urology, Baylor College of Medicine, Houston, Texas. FAU - Rosenfeld, Jill A AU - Rosenfeld JA AD - Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, Washington. FAU - Lipshultz, Larry I AU - Lipshultz LI AD - Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas; Scott Department of Urology, Baylor College of Medicine, Houston, Texas.