MP84-15 LOSS-OF-FUNCTION MISSENSE MUTATIONS IN DCC IDENTIFIED FROM LIFELONG PREMATURE EJACULATION BY TRIO-BASED GENOME SEQUENCING

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP84)1 Apr 2020MP84-15 LOSS-OF-FUNCTION MISSENSE MUTATIONS IN DCC IDENTIFIED FROM LIFELONG PREMATURE EJACULATION BY TRIO-BASED GENOME SEQUENCING Le Ling, Daoqi Wang, Jihong Liu, and Wang Jiaxin* Le LingLe Ling More articles by this author , Daoqi WangDaoqi Wang More articles by this author , Jihong LiuJihong Liu More articles by this author , and Wang Jiaxin*Wang Jiaxin* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000976.015AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Premature ejaculation (PE) is one of the most common sexual dysfunctions and shows genetic predisposition. In this study, we aimed at exploring the mutation spectrum of lifelong PE in Chinese males. METHODS: Through trio-based genome sequencing of 8 trios which included lifelong PE probands and their unaffected parents, we identified four missense mutations of DCC in two trios. Then we amplified the CDS sequences in DCC from lifelong PE patients and inserted them into pCMV plasmids. 293T and cos7 cells were transfected with these plasmids, followed by RT-PCR and Western-blot to investigate the mutant protein expression. Furthermore, we analyzed the functional effect of mutant protein with Netrin-1 treatment. RESULTS: We identified four missense mutations in DCC(p.Val754Met, p.Arg1227His, p.Thr1255Met, p.Pro1281Leu) in lifelong PE. The missense mutations of DCC downregulated the protein expression in 293T and cos7 cells and impaired the binding with Netrin-1, which might cause the change of the protein function. CONCLUSIONS: In this study, we identified four loss-of-function missense mutations in DCC from lifelong PE, which might be an important role in pathogenic mechanism study of lifelong PE. Source of Funding: The National Natural Science Foundation of China © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1270-e1270 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Le Ling More articles by this author Daoqi Wang More articles by this author Jihong Liu More articles by this author Wang Jiaxin* More articles by this author Expand All Advertisement PDF downloadLoading ...